inquinamento ambientale come trigger di …...inquinamento ambientale come trigger di autoimmunità...
TRANSCRIPT
Inquinamento Ambientale
come trigger di
Autoimmunitagrave Endocrina
dal Diabete Mellito alle
Patologie Malassorbitive
Rosaria Maddalena Ruggeri
UNIVERSITArsquo DI MESSINA
DIPARTIMENTO DI MEDICINA CLINICA E SPERIMENTALE
UOC DI ENDOCRINOLOGIA
MALATTIE AUTOIMMUNI
Tireopatie autoimmuni(tiroidite cronica morbo di Basedow)
Diabete mellito tipo 1
Morbo di Addison
Ipofisite
Insufficienza ovarica precoce
Ipoparatiroidismo autoimmune
Endocrino-metaboliche
Malattia Celiaca
Infllammatory bowel disease (IBD)
Gastrite atrofica
Cirrosi biliare primitiva
Epatite autoimmune
Anemia perniciosaTrombocitopenia
Malattie cutanee (Vitiligine Alopecia Penfigo Psoriasi hellip)
Orticaria cronica idiopatica
Malattie reumatiche (S Sjogren Artrite Reumatoide LES Sclerodermiahellip)
Malattie neurologiche (Miastenia grave Sclerosi Multiplahellip)
Non-endocrine
Ersquo comune lrsquoassociazione di piugrave patologie autoimmuni
Ruggeri RM et al Autoimmune comorbidities in Hashimotos thyroiditis different patterns of association
in adulthood and childhoodadolescence Eur J Endocrinol 2017176133-41
MALATTIE AUTOIMMUNI Etiopatogenesi Malattie infiammatorie croniche ad etiopatogenesi multifattoriale
Fattori geneticiHLA
non-HLA- CTLA-4 PD-1L- PTPN22 IL2RA FOXP3- AIRE- CD40 FCLR3- Geni tessuto-specifici
Immunitagrave
adattativa
Fattori
ambientali
esogeni
endogeni
Etnia
Sesso
Etagrave
Ormoni sessuali
Gravidanza
Agenti infettivi
Inquinanti ambientali
Radiazioni ionizzanti
Igiene
Farmaci
Nutrienti (iodio selenio hellip)
Microbiota intestinale
Vitamina D
Stress
FumoAlcol
MALATTIE AUTOIMMUNI Geo-epidemiologia
Negli ultimi 30 anni la prevalenza e incidenza di malattie autoimmuni egrave aumentata significativamente soprattutto nei paesi occidentali
Lerner A et al 2015 Int J celiac disease 3 151-55
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
Migliori standard igienico-sanitari
Disregolazione del sistema immunitario
alterazione del sistema TregBreg e
dellrsquoequilibrio Th1Th2Th17
The hygiene hypothesis
Kondrashova et al The Hygiene hypothesis and the sharp
gradient in the incidence of autoimmune and allergic diseases
between Russian Karelia and Finland APMIS 2013
Bach JF et al The hygiene hypothesis an explanation for the
increased frequency of insulin-dependent diabetes
Cold Spring Harb Perspect Med 2012
Kondrashova et al Serological evidence of thyroid autoimmunity
among schoolchildren in two different socioeconomic
environmentsJ Clin Endocrinolo Metab 2008
Kondrashova et al Lower economic status and inferior hygienic
environment may protect against celiac disease Ann Med 2008
Aumento di MALATTIE
AUTOIMMUNI E ALLERGICHE
Ridotta esposizione a patogeni
in etagrave pediatrica
DISBIOSI
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI
FATTORI AMBIENTALI
The hygiene hypothesisINQUINAMENTO
The consequences of the loss of the Old Friends and distortion of the microbiota are
aggravated by other modern environmental changes that also lead to enhanced
inflammatory responses (pollution (dioxins) changes in dietetc)
laquomicrobial deprivation hypothesisraquo
Inquinanti ambientali Contaminano il terreno le acque e lrsquoaria
Persistono a lungo nellrsquoambiente
Vengono incorporati nelle piante e nelle coltivazioni
Si accumulano nei tessuti animali e nei pesci entrando nella catena alimentare BIOMAGNIFICAZIONE
Sono contenuti in oggetti di uso quotidiano
Esposizione per ingestione inalazione e contatto
laquoEFFETTO COKTAILraquo esposizione combinata a piugrave inquinanti
INQUINANTI AMBIENTALI Utilizzo Esposizione
Bifenili policlorurati (PCBs) e diossine
Fluidi dielettrici e refrigeranti lubrificanti
vernici isolanti ritardanti di fiamma prodotti
di combustione anti-parassitari erbicidi hellip
Inalazione contatto cutaneo
Ingestione - bioaccumulo nella catena
alimentare
Diclorodifeniltricloroetano (DDT)
Diclorodifenildicloroetilene (DDE)
Insetticidi Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ritardanti di fiamma
brominati (BFR e PDBE)
Ignifughi
plastiche vernici fibre sintetiche
elettronica giocattoli mobili imbottiture di
divani materassi sedili auto seggiolini
inalazione
ingestione ndash bioaccumulo nella catena
alimentare (pesce e selvaggina)
Sostanze alchiliche perfluorurate
(PFAS)
Impermeabilizzanti per superfici schiuma
antincendio tessuti utensili da cucina
contenitori e imballaggi per alimenti
Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ftalati Plastificantisolventi
vernici colori cancelleria giocattoli contenitori
e imballaggi per alimenti cosmetici
detergenti smalti adesivi pesticidi
Inalazione di polveri
Ingestione di alimenti contaminati
Contatto cutaneo
Bisfenolo A (BPA) Plastiche e resine
bottiglie per bibite con vuoto a rendere
biberon stoviglie di plastica (piatti e tazze) e
contenitori per alimenti
Ingestione di alimenti contaminati
Metalli pesanti (arsenico
piombo mercurio hellip)
Combustibili attivitagrave industriali Ingestione di acqua e alimenti
contaminati inalazione
Endocrine disruptors
Endocrine disruptors
Endocrine disruptors
Fluidi dielettrici e refrigeranti lubrificanti vernici isolanti ritardanti di
fiamma prodotti di combustione anti-parassitari pesticidi erbicidi
inchiostri hellip
Persistono a lungo nellrsquoambiente
Inquinanti ambientali e autoimmunitagraveBIFENILI POLICLORURATI (PCBs) E DIOSSINE
BIOMAGNIFICAZIONE
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
MALATTIE AUTOIMMUNI
Tireopatie autoimmuni(tiroidite cronica morbo di Basedow)
Diabete mellito tipo 1
Morbo di Addison
Ipofisite
Insufficienza ovarica precoce
Ipoparatiroidismo autoimmune
Endocrino-metaboliche
Malattia Celiaca
Infllammatory bowel disease (IBD)
Gastrite atrofica
Cirrosi biliare primitiva
Epatite autoimmune
Anemia perniciosaTrombocitopenia
Malattie cutanee (Vitiligine Alopecia Penfigo Psoriasi hellip)
Orticaria cronica idiopatica
Malattie reumatiche (S Sjogren Artrite Reumatoide LES Sclerodermiahellip)
Malattie neurologiche (Miastenia grave Sclerosi Multiplahellip)
Non-endocrine
Ersquo comune lrsquoassociazione di piugrave patologie autoimmuni
Ruggeri RM et al Autoimmune comorbidities in Hashimotos thyroiditis different patterns of association
in adulthood and childhoodadolescence Eur J Endocrinol 2017176133-41
MALATTIE AUTOIMMUNI Etiopatogenesi Malattie infiammatorie croniche ad etiopatogenesi multifattoriale
Fattori geneticiHLA
non-HLA- CTLA-4 PD-1L- PTPN22 IL2RA FOXP3- AIRE- CD40 FCLR3- Geni tessuto-specifici
Immunitagrave
adattativa
Fattori
ambientali
esogeni
endogeni
Etnia
Sesso
Etagrave
Ormoni sessuali
Gravidanza
Agenti infettivi
Inquinanti ambientali
Radiazioni ionizzanti
Igiene
Farmaci
Nutrienti (iodio selenio hellip)
Microbiota intestinale
Vitamina D
Stress
FumoAlcol
MALATTIE AUTOIMMUNI Geo-epidemiologia
Negli ultimi 30 anni la prevalenza e incidenza di malattie autoimmuni egrave aumentata significativamente soprattutto nei paesi occidentali
Lerner A et al 2015 Int J celiac disease 3 151-55
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
Migliori standard igienico-sanitari
Disregolazione del sistema immunitario
alterazione del sistema TregBreg e
dellrsquoequilibrio Th1Th2Th17
The hygiene hypothesis
Kondrashova et al The Hygiene hypothesis and the sharp
gradient in the incidence of autoimmune and allergic diseases
between Russian Karelia and Finland APMIS 2013
Bach JF et al The hygiene hypothesis an explanation for the
increased frequency of insulin-dependent diabetes
Cold Spring Harb Perspect Med 2012
Kondrashova et al Serological evidence of thyroid autoimmunity
among schoolchildren in two different socioeconomic
environmentsJ Clin Endocrinolo Metab 2008
Kondrashova et al Lower economic status and inferior hygienic
environment may protect against celiac disease Ann Med 2008
Aumento di MALATTIE
AUTOIMMUNI E ALLERGICHE
Ridotta esposizione a patogeni
in etagrave pediatrica
DISBIOSI
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI
FATTORI AMBIENTALI
The hygiene hypothesisINQUINAMENTO
The consequences of the loss of the Old Friends and distortion of the microbiota are
aggravated by other modern environmental changes that also lead to enhanced
inflammatory responses (pollution (dioxins) changes in dietetc)
laquomicrobial deprivation hypothesisraquo
Inquinanti ambientali Contaminano il terreno le acque e lrsquoaria
Persistono a lungo nellrsquoambiente
Vengono incorporati nelle piante e nelle coltivazioni
Si accumulano nei tessuti animali e nei pesci entrando nella catena alimentare BIOMAGNIFICAZIONE
Sono contenuti in oggetti di uso quotidiano
Esposizione per ingestione inalazione e contatto
laquoEFFETTO COKTAILraquo esposizione combinata a piugrave inquinanti
INQUINANTI AMBIENTALI Utilizzo Esposizione
Bifenili policlorurati (PCBs) e diossine
Fluidi dielettrici e refrigeranti lubrificanti
vernici isolanti ritardanti di fiamma prodotti
di combustione anti-parassitari erbicidi hellip
Inalazione contatto cutaneo
Ingestione - bioaccumulo nella catena
alimentare
Diclorodifeniltricloroetano (DDT)
Diclorodifenildicloroetilene (DDE)
Insetticidi Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ritardanti di fiamma
brominati (BFR e PDBE)
Ignifughi
plastiche vernici fibre sintetiche
elettronica giocattoli mobili imbottiture di
divani materassi sedili auto seggiolini
inalazione
ingestione ndash bioaccumulo nella catena
alimentare (pesce e selvaggina)
Sostanze alchiliche perfluorurate
(PFAS)
Impermeabilizzanti per superfici schiuma
antincendio tessuti utensili da cucina
contenitori e imballaggi per alimenti
Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ftalati Plastificantisolventi
vernici colori cancelleria giocattoli contenitori
e imballaggi per alimenti cosmetici
detergenti smalti adesivi pesticidi
Inalazione di polveri
Ingestione di alimenti contaminati
Contatto cutaneo
Bisfenolo A (BPA) Plastiche e resine
bottiglie per bibite con vuoto a rendere
biberon stoviglie di plastica (piatti e tazze) e
contenitori per alimenti
Ingestione di alimenti contaminati
Metalli pesanti (arsenico
piombo mercurio hellip)
Combustibili attivitagrave industriali Ingestione di acqua e alimenti
contaminati inalazione
Endocrine disruptors
Endocrine disruptors
Endocrine disruptors
Fluidi dielettrici e refrigeranti lubrificanti vernici isolanti ritardanti di
fiamma prodotti di combustione anti-parassitari pesticidi erbicidi
inchiostri hellip
Persistono a lungo nellrsquoambiente
Inquinanti ambientali e autoimmunitagraveBIFENILI POLICLORURATI (PCBs) E DIOSSINE
BIOMAGNIFICAZIONE
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
MALATTIE AUTOIMMUNI Etiopatogenesi Malattie infiammatorie croniche ad etiopatogenesi multifattoriale
Fattori geneticiHLA
non-HLA- CTLA-4 PD-1L- PTPN22 IL2RA FOXP3- AIRE- CD40 FCLR3- Geni tessuto-specifici
Immunitagrave
adattativa
Fattori
ambientali
esogeni
endogeni
Etnia
Sesso
Etagrave
Ormoni sessuali
Gravidanza
Agenti infettivi
Inquinanti ambientali
Radiazioni ionizzanti
Igiene
Farmaci
Nutrienti (iodio selenio hellip)
Microbiota intestinale
Vitamina D
Stress
FumoAlcol
MALATTIE AUTOIMMUNI Geo-epidemiologia
Negli ultimi 30 anni la prevalenza e incidenza di malattie autoimmuni egrave aumentata significativamente soprattutto nei paesi occidentali
Lerner A et al 2015 Int J celiac disease 3 151-55
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
Migliori standard igienico-sanitari
Disregolazione del sistema immunitario
alterazione del sistema TregBreg e
dellrsquoequilibrio Th1Th2Th17
The hygiene hypothesis
Kondrashova et al The Hygiene hypothesis and the sharp
gradient in the incidence of autoimmune and allergic diseases
between Russian Karelia and Finland APMIS 2013
Bach JF et al The hygiene hypothesis an explanation for the
increased frequency of insulin-dependent diabetes
Cold Spring Harb Perspect Med 2012
Kondrashova et al Serological evidence of thyroid autoimmunity
among schoolchildren in two different socioeconomic
environmentsJ Clin Endocrinolo Metab 2008
Kondrashova et al Lower economic status and inferior hygienic
environment may protect against celiac disease Ann Med 2008
Aumento di MALATTIE
AUTOIMMUNI E ALLERGICHE
Ridotta esposizione a patogeni
in etagrave pediatrica
DISBIOSI
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI
FATTORI AMBIENTALI
The hygiene hypothesisINQUINAMENTO
The consequences of the loss of the Old Friends and distortion of the microbiota are
aggravated by other modern environmental changes that also lead to enhanced
inflammatory responses (pollution (dioxins) changes in dietetc)
laquomicrobial deprivation hypothesisraquo
Inquinanti ambientali Contaminano il terreno le acque e lrsquoaria
Persistono a lungo nellrsquoambiente
Vengono incorporati nelle piante e nelle coltivazioni
Si accumulano nei tessuti animali e nei pesci entrando nella catena alimentare BIOMAGNIFICAZIONE
Sono contenuti in oggetti di uso quotidiano
Esposizione per ingestione inalazione e contatto
laquoEFFETTO COKTAILraquo esposizione combinata a piugrave inquinanti
INQUINANTI AMBIENTALI Utilizzo Esposizione
Bifenili policlorurati (PCBs) e diossine
Fluidi dielettrici e refrigeranti lubrificanti
vernici isolanti ritardanti di fiamma prodotti
di combustione anti-parassitari erbicidi hellip
Inalazione contatto cutaneo
Ingestione - bioaccumulo nella catena
alimentare
Diclorodifeniltricloroetano (DDT)
Diclorodifenildicloroetilene (DDE)
Insetticidi Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ritardanti di fiamma
brominati (BFR e PDBE)
Ignifughi
plastiche vernici fibre sintetiche
elettronica giocattoli mobili imbottiture di
divani materassi sedili auto seggiolini
inalazione
ingestione ndash bioaccumulo nella catena
alimentare (pesce e selvaggina)
Sostanze alchiliche perfluorurate
(PFAS)
Impermeabilizzanti per superfici schiuma
antincendio tessuti utensili da cucina
contenitori e imballaggi per alimenti
Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ftalati Plastificantisolventi
vernici colori cancelleria giocattoli contenitori
e imballaggi per alimenti cosmetici
detergenti smalti adesivi pesticidi
Inalazione di polveri
Ingestione di alimenti contaminati
Contatto cutaneo
Bisfenolo A (BPA) Plastiche e resine
bottiglie per bibite con vuoto a rendere
biberon stoviglie di plastica (piatti e tazze) e
contenitori per alimenti
Ingestione di alimenti contaminati
Metalli pesanti (arsenico
piombo mercurio hellip)
Combustibili attivitagrave industriali Ingestione di acqua e alimenti
contaminati inalazione
Endocrine disruptors
Endocrine disruptors
Endocrine disruptors
Fluidi dielettrici e refrigeranti lubrificanti vernici isolanti ritardanti di
fiamma prodotti di combustione anti-parassitari pesticidi erbicidi
inchiostri hellip
Persistono a lungo nellrsquoambiente
Inquinanti ambientali e autoimmunitagraveBIFENILI POLICLORURATI (PCBs) E DIOSSINE
BIOMAGNIFICAZIONE
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
MALATTIE AUTOIMMUNI Geo-epidemiologia
Negli ultimi 30 anni la prevalenza e incidenza di malattie autoimmuni egrave aumentata significativamente soprattutto nei paesi occidentali
Lerner A et al 2015 Int J celiac disease 3 151-55
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
Migliori standard igienico-sanitari
Disregolazione del sistema immunitario
alterazione del sistema TregBreg e
dellrsquoequilibrio Th1Th2Th17
The hygiene hypothesis
Kondrashova et al The Hygiene hypothesis and the sharp
gradient in the incidence of autoimmune and allergic diseases
between Russian Karelia and Finland APMIS 2013
Bach JF et al The hygiene hypothesis an explanation for the
increased frequency of insulin-dependent diabetes
Cold Spring Harb Perspect Med 2012
Kondrashova et al Serological evidence of thyroid autoimmunity
among schoolchildren in two different socioeconomic
environmentsJ Clin Endocrinolo Metab 2008
Kondrashova et al Lower economic status and inferior hygienic
environment may protect against celiac disease Ann Med 2008
Aumento di MALATTIE
AUTOIMMUNI E ALLERGICHE
Ridotta esposizione a patogeni
in etagrave pediatrica
DISBIOSI
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI
FATTORI AMBIENTALI
The hygiene hypothesisINQUINAMENTO
The consequences of the loss of the Old Friends and distortion of the microbiota are
aggravated by other modern environmental changes that also lead to enhanced
inflammatory responses (pollution (dioxins) changes in dietetc)
laquomicrobial deprivation hypothesisraquo
Inquinanti ambientali Contaminano il terreno le acque e lrsquoaria
Persistono a lungo nellrsquoambiente
Vengono incorporati nelle piante e nelle coltivazioni
Si accumulano nei tessuti animali e nei pesci entrando nella catena alimentare BIOMAGNIFICAZIONE
Sono contenuti in oggetti di uso quotidiano
Esposizione per ingestione inalazione e contatto
laquoEFFETTO COKTAILraquo esposizione combinata a piugrave inquinanti
INQUINANTI AMBIENTALI Utilizzo Esposizione
Bifenili policlorurati (PCBs) e diossine
Fluidi dielettrici e refrigeranti lubrificanti
vernici isolanti ritardanti di fiamma prodotti
di combustione anti-parassitari erbicidi hellip
Inalazione contatto cutaneo
Ingestione - bioaccumulo nella catena
alimentare
Diclorodifeniltricloroetano (DDT)
Diclorodifenildicloroetilene (DDE)
Insetticidi Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ritardanti di fiamma
brominati (BFR e PDBE)
Ignifughi
plastiche vernici fibre sintetiche
elettronica giocattoli mobili imbottiture di
divani materassi sedili auto seggiolini
inalazione
ingestione ndash bioaccumulo nella catena
alimentare (pesce e selvaggina)
Sostanze alchiliche perfluorurate
(PFAS)
Impermeabilizzanti per superfici schiuma
antincendio tessuti utensili da cucina
contenitori e imballaggi per alimenti
Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ftalati Plastificantisolventi
vernici colori cancelleria giocattoli contenitori
e imballaggi per alimenti cosmetici
detergenti smalti adesivi pesticidi
Inalazione di polveri
Ingestione di alimenti contaminati
Contatto cutaneo
Bisfenolo A (BPA) Plastiche e resine
bottiglie per bibite con vuoto a rendere
biberon stoviglie di plastica (piatti e tazze) e
contenitori per alimenti
Ingestione di alimenti contaminati
Metalli pesanti (arsenico
piombo mercurio hellip)
Combustibili attivitagrave industriali Ingestione di acqua e alimenti
contaminati inalazione
Endocrine disruptors
Endocrine disruptors
Endocrine disruptors
Fluidi dielettrici e refrigeranti lubrificanti vernici isolanti ritardanti di
fiamma prodotti di combustione anti-parassitari pesticidi erbicidi
inchiostri hellip
Persistono a lungo nellrsquoambiente
Inquinanti ambientali e autoimmunitagraveBIFENILI POLICLORURATI (PCBs) E DIOSSINE
BIOMAGNIFICAZIONE
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
Migliori standard igienico-sanitari
Disregolazione del sistema immunitario
alterazione del sistema TregBreg e
dellrsquoequilibrio Th1Th2Th17
The hygiene hypothesis
Kondrashova et al The Hygiene hypothesis and the sharp
gradient in the incidence of autoimmune and allergic diseases
between Russian Karelia and Finland APMIS 2013
Bach JF et al The hygiene hypothesis an explanation for the
increased frequency of insulin-dependent diabetes
Cold Spring Harb Perspect Med 2012
Kondrashova et al Serological evidence of thyroid autoimmunity
among schoolchildren in two different socioeconomic
environmentsJ Clin Endocrinolo Metab 2008
Kondrashova et al Lower economic status and inferior hygienic
environment may protect against celiac disease Ann Med 2008
Aumento di MALATTIE
AUTOIMMUNI E ALLERGICHE
Ridotta esposizione a patogeni
in etagrave pediatrica
DISBIOSI
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI
FATTORI AMBIENTALI
The hygiene hypothesisINQUINAMENTO
The consequences of the loss of the Old Friends and distortion of the microbiota are
aggravated by other modern environmental changes that also lead to enhanced
inflammatory responses (pollution (dioxins) changes in dietetc)
laquomicrobial deprivation hypothesisraquo
Inquinanti ambientali Contaminano il terreno le acque e lrsquoaria
Persistono a lungo nellrsquoambiente
Vengono incorporati nelle piante e nelle coltivazioni
Si accumulano nei tessuti animali e nei pesci entrando nella catena alimentare BIOMAGNIFICAZIONE
Sono contenuti in oggetti di uso quotidiano
Esposizione per ingestione inalazione e contatto
laquoEFFETTO COKTAILraquo esposizione combinata a piugrave inquinanti
INQUINANTI AMBIENTALI Utilizzo Esposizione
Bifenili policlorurati (PCBs) e diossine
Fluidi dielettrici e refrigeranti lubrificanti
vernici isolanti ritardanti di fiamma prodotti
di combustione anti-parassitari erbicidi hellip
Inalazione contatto cutaneo
Ingestione - bioaccumulo nella catena
alimentare
Diclorodifeniltricloroetano (DDT)
Diclorodifenildicloroetilene (DDE)
Insetticidi Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ritardanti di fiamma
brominati (BFR e PDBE)
Ignifughi
plastiche vernici fibre sintetiche
elettronica giocattoli mobili imbottiture di
divani materassi sedili auto seggiolini
inalazione
ingestione ndash bioaccumulo nella catena
alimentare (pesce e selvaggina)
Sostanze alchiliche perfluorurate
(PFAS)
Impermeabilizzanti per superfici schiuma
antincendio tessuti utensili da cucina
contenitori e imballaggi per alimenti
Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ftalati Plastificantisolventi
vernici colori cancelleria giocattoli contenitori
e imballaggi per alimenti cosmetici
detergenti smalti adesivi pesticidi
Inalazione di polveri
Ingestione di alimenti contaminati
Contatto cutaneo
Bisfenolo A (BPA) Plastiche e resine
bottiglie per bibite con vuoto a rendere
biberon stoviglie di plastica (piatti e tazze) e
contenitori per alimenti
Ingestione di alimenti contaminati
Metalli pesanti (arsenico
piombo mercurio hellip)
Combustibili attivitagrave industriali Ingestione di acqua e alimenti
contaminati inalazione
Endocrine disruptors
Endocrine disruptors
Endocrine disruptors
Fluidi dielettrici e refrigeranti lubrificanti vernici isolanti ritardanti di
fiamma prodotti di combustione anti-parassitari pesticidi erbicidi
inchiostri hellip
Persistono a lungo nellrsquoambiente
Inquinanti ambientali e autoimmunitagraveBIFENILI POLICLORURATI (PCBs) E DIOSSINE
BIOMAGNIFICAZIONE
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Migliori standard igienico-sanitari
Disregolazione del sistema immunitario
alterazione del sistema TregBreg e
dellrsquoequilibrio Th1Th2Th17
The hygiene hypothesis
Kondrashova et al The Hygiene hypothesis and the sharp
gradient in the incidence of autoimmune and allergic diseases
between Russian Karelia and Finland APMIS 2013
Bach JF et al The hygiene hypothesis an explanation for the
increased frequency of insulin-dependent diabetes
Cold Spring Harb Perspect Med 2012
Kondrashova et al Serological evidence of thyroid autoimmunity
among schoolchildren in two different socioeconomic
environmentsJ Clin Endocrinolo Metab 2008
Kondrashova et al Lower economic status and inferior hygienic
environment may protect against celiac disease Ann Med 2008
Aumento di MALATTIE
AUTOIMMUNI E ALLERGICHE
Ridotta esposizione a patogeni
in etagrave pediatrica
DISBIOSI
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI
FATTORI AMBIENTALI
The hygiene hypothesisINQUINAMENTO
The consequences of the loss of the Old Friends and distortion of the microbiota are
aggravated by other modern environmental changes that also lead to enhanced
inflammatory responses (pollution (dioxins) changes in dietetc)
laquomicrobial deprivation hypothesisraquo
Inquinanti ambientali Contaminano il terreno le acque e lrsquoaria
Persistono a lungo nellrsquoambiente
Vengono incorporati nelle piante e nelle coltivazioni
Si accumulano nei tessuti animali e nei pesci entrando nella catena alimentare BIOMAGNIFICAZIONE
Sono contenuti in oggetti di uso quotidiano
Esposizione per ingestione inalazione e contatto
laquoEFFETTO COKTAILraquo esposizione combinata a piugrave inquinanti
INQUINANTI AMBIENTALI Utilizzo Esposizione
Bifenili policlorurati (PCBs) e diossine
Fluidi dielettrici e refrigeranti lubrificanti
vernici isolanti ritardanti di fiamma prodotti
di combustione anti-parassitari erbicidi hellip
Inalazione contatto cutaneo
Ingestione - bioaccumulo nella catena
alimentare
Diclorodifeniltricloroetano (DDT)
Diclorodifenildicloroetilene (DDE)
Insetticidi Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ritardanti di fiamma
brominati (BFR e PDBE)
Ignifughi
plastiche vernici fibre sintetiche
elettronica giocattoli mobili imbottiture di
divani materassi sedili auto seggiolini
inalazione
ingestione ndash bioaccumulo nella catena
alimentare (pesce e selvaggina)
Sostanze alchiliche perfluorurate
(PFAS)
Impermeabilizzanti per superfici schiuma
antincendio tessuti utensili da cucina
contenitori e imballaggi per alimenti
Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ftalati Plastificantisolventi
vernici colori cancelleria giocattoli contenitori
e imballaggi per alimenti cosmetici
detergenti smalti adesivi pesticidi
Inalazione di polveri
Ingestione di alimenti contaminati
Contatto cutaneo
Bisfenolo A (BPA) Plastiche e resine
bottiglie per bibite con vuoto a rendere
biberon stoviglie di plastica (piatti e tazze) e
contenitori per alimenti
Ingestione di alimenti contaminati
Metalli pesanti (arsenico
piombo mercurio hellip)
Combustibili attivitagrave industriali Ingestione di acqua e alimenti
contaminati inalazione
Endocrine disruptors
Endocrine disruptors
Endocrine disruptors
Fluidi dielettrici e refrigeranti lubrificanti vernici isolanti ritardanti di
fiamma prodotti di combustione anti-parassitari pesticidi erbicidi
inchiostri hellip
Persistono a lungo nellrsquoambiente
Inquinanti ambientali e autoimmunitagraveBIFENILI POLICLORURATI (PCBs) E DIOSSINE
BIOMAGNIFICAZIONE
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI
FATTORI AMBIENTALI
The hygiene hypothesisINQUINAMENTO
The consequences of the loss of the Old Friends and distortion of the microbiota are
aggravated by other modern environmental changes that also lead to enhanced
inflammatory responses (pollution (dioxins) changes in dietetc)
laquomicrobial deprivation hypothesisraquo
Inquinanti ambientali Contaminano il terreno le acque e lrsquoaria
Persistono a lungo nellrsquoambiente
Vengono incorporati nelle piante e nelle coltivazioni
Si accumulano nei tessuti animali e nei pesci entrando nella catena alimentare BIOMAGNIFICAZIONE
Sono contenuti in oggetti di uso quotidiano
Esposizione per ingestione inalazione e contatto
laquoEFFETTO COKTAILraquo esposizione combinata a piugrave inquinanti
INQUINANTI AMBIENTALI Utilizzo Esposizione
Bifenili policlorurati (PCBs) e diossine
Fluidi dielettrici e refrigeranti lubrificanti
vernici isolanti ritardanti di fiamma prodotti
di combustione anti-parassitari erbicidi hellip
Inalazione contatto cutaneo
Ingestione - bioaccumulo nella catena
alimentare
Diclorodifeniltricloroetano (DDT)
Diclorodifenildicloroetilene (DDE)
Insetticidi Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ritardanti di fiamma
brominati (BFR e PDBE)
Ignifughi
plastiche vernici fibre sintetiche
elettronica giocattoli mobili imbottiture di
divani materassi sedili auto seggiolini
inalazione
ingestione ndash bioaccumulo nella catena
alimentare (pesce e selvaggina)
Sostanze alchiliche perfluorurate
(PFAS)
Impermeabilizzanti per superfici schiuma
antincendio tessuti utensili da cucina
contenitori e imballaggi per alimenti
Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ftalati Plastificantisolventi
vernici colori cancelleria giocattoli contenitori
e imballaggi per alimenti cosmetici
detergenti smalti adesivi pesticidi
Inalazione di polveri
Ingestione di alimenti contaminati
Contatto cutaneo
Bisfenolo A (BPA) Plastiche e resine
bottiglie per bibite con vuoto a rendere
biberon stoviglie di plastica (piatti e tazze) e
contenitori per alimenti
Ingestione di alimenti contaminati
Metalli pesanti (arsenico
piombo mercurio hellip)
Combustibili attivitagrave industriali Ingestione di acqua e alimenti
contaminati inalazione
Endocrine disruptors
Endocrine disruptors
Endocrine disruptors
Fluidi dielettrici e refrigeranti lubrificanti vernici isolanti ritardanti di
fiamma prodotti di combustione anti-parassitari pesticidi erbicidi
inchiostri hellip
Persistono a lungo nellrsquoambiente
Inquinanti ambientali e autoimmunitagraveBIFENILI POLICLORURATI (PCBs) E DIOSSINE
BIOMAGNIFICAZIONE
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Inquinanti ambientali Contaminano il terreno le acque e lrsquoaria
Persistono a lungo nellrsquoambiente
Vengono incorporati nelle piante e nelle coltivazioni
Si accumulano nei tessuti animali e nei pesci entrando nella catena alimentare BIOMAGNIFICAZIONE
Sono contenuti in oggetti di uso quotidiano
Esposizione per ingestione inalazione e contatto
laquoEFFETTO COKTAILraquo esposizione combinata a piugrave inquinanti
INQUINANTI AMBIENTALI Utilizzo Esposizione
Bifenili policlorurati (PCBs) e diossine
Fluidi dielettrici e refrigeranti lubrificanti
vernici isolanti ritardanti di fiamma prodotti
di combustione anti-parassitari erbicidi hellip
Inalazione contatto cutaneo
Ingestione - bioaccumulo nella catena
alimentare
Diclorodifeniltricloroetano (DDT)
Diclorodifenildicloroetilene (DDE)
Insetticidi Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ritardanti di fiamma
brominati (BFR e PDBE)
Ignifughi
plastiche vernici fibre sintetiche
elettronica giocattoli mobili imbottiture di
divani materassi sedili auto seggiolini
inalazione
ingestione ndash bioaccumulo nella catena
alimentare (pesce e selvaggina)
Sostanze alchiliche perfluorurate
(PFAS)
Impermeabilizzanti per superfici schiuma
antincendio tessuti utensili da cucina
contenitori e imballaggi per alimenti
Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ftalati Plastificantisolventi
vernici colori cancelleria giocattoli contenitori
e imballaggi per alimenti cosmetici
detergenti smalti adesivi pesticidi
Inalazione di polveri
Ingestione di alimenti contaminati
Contatto cutaneo
Bisfenolo A (BPA) Plastiche e resine
bottiglie per bibite con vuoto a rendere
biberon stoviglie di plastica (piatti e tazze) e
contenitori per alimenti
Ingestione di alimenti contaminati
Metalli pesanti (arsenico
piombo mercurio hellip)
Combustibili attivitagrave industriali Ingestione di acqua e alimenti
contaminati inalazione
Endocrine disruptors
Endocrine disruptors
Endocrine disruptors
Fluidi dielettrici e refrigeranti lubrificanti vernici isolanti ritardanti di
fiamma prodotti di combustione anti-parassitari pesticidi erbicidi
inchiostri hellip
Persistono a lungo nellrsquoambiente
Inquinanti ambientali e autoimmunitagraveBIFENILI POLICLORURATI (PCBs) E DIOSSINE
BIOMAGNIFICAZIONE
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
INQUINANTI AMBIENTALI Utilizzo Esposizione
Bifenili policlorurati (PCBs) e diossine
Fluidi dielettrici e refrigeranti lubrificanti
vernici isolanti ritardanti di fiamma prodotti
di combustione anti-parassitari erbicidi hellip
Inalazione contatto cutaneo
Ingestione - bioaccumulo nella catena
alimentare
Diclorodifeniltricloroetano (DDT)
Diclorodifenildicloroetilene (DDE)
Insetticidi Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ritardanti di fiamma
brominati (BFR e PDBE)
Ignifughi
plastiche vernici fibre sintetiche
elettronica giocattoli mobili imbottiture di
divani materassi sedili auto seggiolini
inalazione
ingestione ndash bioaccumulo nella catena
alimentare (pesce e selvaggina)
Sostanze alchiliche perfluorurate
(PFAS)
Impermeabilizzanti per superfici schiuma
antincendio tessuti utensili da cucina
contenitori e imballaggi per alimenti
Ingestione - bioaccumulo nella catena
alimentare (pesce e selvaggina)
Ftalati Plastificantisolventi
vernici colori cancelleria giocattoli contenitori
e imballaggi per alimenti cosmetici
detergenti smalti adesivi pesticidi
Inalazione di polveri
Ingestione di alimenti contaminati
Contatto cutaneo
Bisfenolo A (BPA) Plastiche e resine
bottiglie per bibite con vuoto a rendere
biberon stoviglie di plastica (piatti e tazze) e
contenitori per alimenti
Ingestione di alimenti contaminati
Metalli pesanti (arsenico
piombo mercurio hellip)
Combustibili attivitagrave industriali Ingestione di acqua e alimenti
contaminati inalazione
Endocrine disruptors
Endocrine disruptors
Endocrine disruptors
Fluidi dielettrici e refrigeranti lubrificanti vernici isolanti ritardanti di
fiamma prodotti di combustione anti-parassitari pesticidi erbicidi
inchiostri hellip
Persistono a lungo nellrsquoambiente
Inquinanti ambientali e autoimmunitagraveBIFENILI POLICLORURATI (PCBs) E DIOSSINE
BIOMAGNIFICAZIONE
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Fluidi dielettrici e refrigeranti lubrificanti vernici isolanti ritardanti di
fiamma prodotti di combustione anti-parassitari pesticidi erbicidi
inchiostri hellip
Persistono a lungo nellrsquoambiente
Inquinanti ambientali e autoimmunitagraveBIFENILI POLICLORURATI (PCBs) E DIOSSINE
BIOMAGNIFICAZIONE
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Inquinanti e Diabete mellito tipo 1
Bodin J et al Long-term bisphenol A exposure accelerates insulitis development in
diabetes-prone NOD mice Immunopharmacol Immunotoxicol 2013 35(3)349-58
Bodin J et al Transmaternal bisphenol A exposure accelerates diabetes type 1
development in NOD mice Toxicol Sci 2014137(2)311-23
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Hathout EH et al Air pollution and type 1 diabetes in children Pediatr Diabetes
2006781ndash7
Inquinanti e Diabete mellito tipo 1
Bodin J Stene LC Nygaard UC Can exposure to environmental chemicals increase the risk of
diabetes type 1 development Biomed Res Int 20152015208947
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Inquinamento e autoimmunitagrave tiroidea
Freire et al Long-term exposure to organochlorine pesticides and thyroid status in adults in a
heavily contaminated area in Brazil Environ Res 20131277ndash
Freire et al Long term exposure to organochlorine pesticides and thyroid function in children
from Cidade dos Meninos Rio de Janeiro Brazil Environ Res 201211768ndash74
Goldner et al Pesticide use and thyroid disease among women in the Agricultural Health
Study Am J Epidemiol 2010171455ndash64
Raacutedikovaacute et al Possible effects of environmental nitrates and toxic organochlorines on human
thyroid in highly polluted areas in Slovakia Thyroid 200818353ndash62
Schell LM et al Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne
Mohawk young adults Environ Res 200910986ndash92
Langer P et al Increased thyroid volume and prevalence of thyroid disorders in an area heavily
polluted by polychlorinated biphenyls Eur J Endocrinol 1998139402ndash9
Benvenga S et al
Rev Endocr Metab Disord (2015) 16319ndash340
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Aumentata prevalenza di gozzo ed ipoecogenicitagrave in soggetti provenienti da aree
inquinate
P Langer et al Chemosphere 2007 69118ndash127P Langer Frontiers in Neuroendocrinology 2010 31497ndash518
Inquinamento e autoimmunitagrave tiroidea
Aumentata prevalenza di Ab anti-tiroide in soggetti provenienti da aree
inquinate
Plt0001
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Inquinamento e autoimmunitagrave tiroidea
Variabili associate con lo sviluppo di anticorpi anti-tiroide
Arena et al Chronic lymphocytic thyroiditis could it be influenced
by a petrochemical complex Data from a cytological study in South-Eastern Sicily Eur J Endocrinol 2015172383ndash6
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Pgt005
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Chemicals can act directly on beta
or immune cells by binding to
receptors or after uptake in the
cells by pinocytosis endocytosis
or diffusion
Chemicals can affect factors like
mucosal permeability the
microbiome or the hormone
balance all shown to interact with
the immune system
Several chemicals can
induce epigenetic
changes
Bodin et al Biomed Res Int 2015
Inquinamento ambientale e autoimmunitagrave
Meccanismi di azione
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
GUT MICROBIOTA
FATTORI CHE INFLUENZANO IL MICROBIOTA
LrsquoOSPITE LrsquoAMBIENTE
Lozupone CA et al Diversity stability and resilience of the human gut microbiota Nature 2012 489 220-30
Sekirov I et al Gut microbiota in health and disease Physiol Rev 2010 90 859-904
La flora microbica commensale delle mucosa umana il sito piugrave esposto
allrsquoambiente esterno svolge funzioni fondamentali
Integritagrave anatomica e funzionale della barriera intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario rarr immunocompetenza
e tolleranza immunitaria
Catabolismo di xenobiotici e farmaci
profilo genetico
sesso
etagrave
DIETA
INFEZIONI GASTRO-ENTERICHE
FARMACI (antibiotici in medicina e
agricolturaallevamento probiotici prebiotici hellip)
XENOBIOTICI
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
DISBIOSI Alterazioni della composizione del microbiota
Malattie gastroentericheGastrite ulcera peptica
Sindrome dellrsquointestino irritabile
Malattie infiammatorie croniche intestinali (IBD)CeliachiaCancro dello stomaco e del colon
Diverticolosi
Obesitagrave
Insulino-resistenza
Diabete Mellito tipo 2
Integritagrave anatomica e funzionale della barriera
intestinale
Assorbimento nutrienti e metabolismo energetico
Sviluppo e regolazione del sistema immunitario
rarr immunocompetenza e tolleranza
immunitaria
Malattie autoimmuniMalattie allergicheIntolleranze Alimentari
B Chen et al Integration of microbiome and epigenome to decipher the
pathogenesis of autoimmune diseases J Autoimmunity 2017
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Cukrowska B et al Intestinal epithelium intraepithelial lymphocytes and the gut microbiota - Key players in the
pathogenesis of celiac disease World J Gastroenterol 2017237505-18
Inquinanti e Celiachia ruolo del microbiota
Dysbiosis meaning an imbalance in
the gut microbiota and its
metabolome may activate innate
immunity leading to pro-
inflammatory changes which
induces intraepithelial lymphocyte
infiltration and epithelial barrier
damage ultimately resulting in
increased transfer of gluten peptides
and inflammatory activation leading
to CD development
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
POSSIBILI MECCANISMI
Disbiosi
Alterazione barriera intestinale
Inibizione citocromo P450
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
RAPIDO INCREMENTO NEI PAESI INDUSTRIALIZZATI
CHIARA RELAZIONE CON LE CONDIZIONI SOCIO-ECONOMICHE
DATI IN POPOLAZIONI DI MIGRANTI
MALATTIE AUTOIMMUNI Etiopatogenesi
INFEZIONI NUTRIZIONE
INQUINAMENTO
FATTORI AMBIENTALI
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWestern dietraquo lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune Diseases
Curr Allergy Asthma Rep 2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
Environ Health Perspect 2016 1241521ndash28
Participants with high fast food intake had 20ndash40 higher urinary
concentrations of phthalate metabolites than did non-consumers
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
We did find a significant monotonic association between fast food meat
intake and BPA which corresponds to the small but growing evidence
suggesting that hamburgers may be a source of BPA exposure
In a 2008 total diet study in Quebec Canada levels of BPA in fast food
composite samples were generally low (1ndash3 ngg) except for in the
hamburger (109 ngg) (Cao et al 2011)
In a study of 491 Mexican-American pregnant women those who consumed
hamburgers three or more times a week had 20 higher urinary BPA levels
than did nonconsumers of hamburgers (Quiroacutes-Alcalaacute et al 2013)
Environ Health Perspect 2016 1241521ndash28
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
INQUINANTI AMBIENTALI E AUTOIMMUNITArsquo
GLI INQUINANTI AMBIENTALI RAPPRESENTANO TRIGGER DI
AUTOIMMUNITArsquo IN SOGGETTI PREDISPOSTI
POSSONO AVERE EFFETTO ADDITIVO E SINERGISTICO
POSSONO AGIRE CON MECCANISMI DIVERSI E IN FASI
DIVERSE DI SVILUPPO DELLA MALATTIA
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Willebrand et al The role of salt for immune cell function and disease Immunology 2018154(3)346-353
Dolan et al Diet gut microbes and the pathogenesis of inflammatory bowel diseases Molecular
Nutrition amp Food Research 2017 61 (1)
Richards et al Dietary metabolites and the gut microbiota an alternative approach to control inflammatory and
autoimmune diseases Clin Transl Immunology 2016 135(5)e82
Manzel et al Role of ldquoWestern Dietrdquo in Inflammatory Autoimmune Diseases Curr Allergy Asthma
Rep 2014 14 404
NUTRIZIONE e AUTOIMMUNITArsquo
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404
high-fat and cholesterol
high-protein
high-sugar
excess salt intake
frequent consumption of processed and
fast foodslsquo
too many calories
laquoWESTERN DIETraquo
lack of anti-oxidants from fruit and vegetables
systemic inflammation and inflammatory cytokine
upregulation (IL-6TNFἀ)
modulation of immune response (TregTH17 balance)
hormonal effects (leptin resistine)
gut microbiota disruption
Manzel et al Role of ldquoWestern Dietrdquo
in Inflammatory Autoimmune
Diseases Curr Allergy Asthma Rep
2014 14 404