how to diversify a dwindling microbiome to... · 2018-06-15 · how to diversify a dwindling...

How to Diversify a Dwindling Microbiome

Dr Jason A HawrelakND BNat(Hons) PhD FNHAA MASN FACN

Senior Lecturer

School of Medicine UTas

Visiting Research Fellow ARCCIM UTS

ProbioticAdvisorcom

The Human GIT Microbiota

AKA the microflora or GIT ecosystem

Human gut microbiota contains 1014 living microorganisms (Neish 2009)(Lozupone 2012)

bull this may be 10 times the number of cells in the human bodybull from over 1000 different species

bull a mutually beneficial symbiotic relationshipbull a collection of cells that work in unison with the host and that can

promote health but sometimes initiates disease

bull dysbiosis

copy Dr Jason Hawrelak 2018


A vital becoming appreciated human organ

bull the microbiota organweighs 1-2 kg

bull exceeds the liver in thenumber of biochemicalreactions in which itparticipates


What does our Microbiota Organ do for us

bull Xenobiotic metabolismbull polyphenols

bull phytoestrogensbull glycosides

bull Colonisation resistance

bull Production of SCFAs

bull Regulates metabolism

bull Blood glucose control amp insulin sensitivity

bull Mood management

bull Impacts our inflammatory milieu

bull Modulates the immune systembull protects against allergy

development

bull up-regulates non-specific immunity

bull trains our immune system

bull lsquoNormalrsquo gut motility

bull Improves nutritional statusbull B vitamins

bull vitamin K

bull mineral absorption ndash Cal Mg Zn

bull energy salvaging


Diseases Associated with GI Dysbiosis

bull Non-GI Conditions Alzheimerrsquos disease

Anxiety

Asthma

Atopic eczema

Autism

Chronic Fatigue Syndrome

Depression

Kidney stones

Metabolic syndrome

Multiple sclerosis

Obesity

Parkinsonrsquos disease

Rheumatoid arthritis

Type I diabetes

Type II diabetes

bull GI ConditionsAlcoholic liver disease

Antibiotic-associated diarrhoea

Chemotherapy-associated diarrhoea

Clostridium difficile-associated disease

Coeliac disease

Crohnrsquos disease

Diverticular disease

Irritable bowel syndrome

Liver cirrhosis

Non-alcoholic fatty liver disease

Radiotherapy-associated diarrhoea

SIBO

Ulcerative colitis copy Dr Jason Hawrelak 2018

GIT Microbiota

bull Each individualrsquos microbiota is unique (Lozupone Stombaugh Gordon Jansson

amp Knight 2012)

bull some similarities at the phylum level less at the genus level and even less at the species and strain levels

bull closest relatives have the most similar ecologies

bull Each of us harbours around 160 different speciesbull 30-40 species make up the vast bulk of the ecosystem

bull ldquoIdealrdquo microbiota is not known buthellip


Microbiota Diversitybull Diversity - the Spice of Life

bull A diverse colonic microbiota = healthy ecosystem

bull Lack of microbial diversity in the colonic ecosystem associated with (Le Chatelier et al 2013)(Abrahamsson et al 2014)(Abrahamsson et al

2012)(Yurkovetskiy Pickard amp Chervonsky 2015)

bull increased risk of allergies and asthma in children

bull obesity

bull insulin resistance (metabolic syndrome amp type 2 diabetes)

bull dyslipidaemia (high cholesterol and triglycerides)

bull auto-immunity

bull body-wide inflammationcopy Dr Jason Hawrelak 2018

Disappearing Microbiota Hypothesis

bull Hypothesis put forth by Martin Blaser in 2009 (Blaser amp Falkow 2009)

bull Humans and our ancestors have evolved since the most ancient times with a commensal microbiota

bull Through modern medical practices and lifestyle and dietary changes the microbiota in human populations is changing sometimes to an extreme degreebull Clean drinkingbathing water

bull uarr rates of C-sections

bull uarr rates of pre-term and infant AB use

bull Widespread AB use throughout life

bull Reduced breastfeeding rates

bull uarr use of antibacterial soaps creams and sprays

bull Disappearance of our ancestral indigenous organisms which are intimately involved in human physiology is not beneficialand has consequenceshellip



From (Blaser 2017)


The Dwindling Microbiota

bull Factors in early childhood impact the diversity of the microbiota for lifebull Birth ndash C-section vs vaginal

bull Breastfed vs bottle-fed

bull Early childhood AB use

bull AB - frequency of use

bull AB cocktails

bull Early childhood PPI use

bull Maternal factors influence a new childrsquos microbiotabull Whole life AB exposure

bull Frequency of AB use

bull AB cocktail use

bull AB use during pregnancy amp at birth

bull PPI exposure in life amp pregnancy

bull Dysbiosis-inducing andor restrictive diets

bull Food additive and environmental chemical exposure


Antibiotic Use ndash Timing amp Sequelae

bull From (Langdon Crook amp Dantas 2016)


The Results of Microbiota Diversity Loss

bull From (van de Guchte et al 2018)copy Dr Jason Hawrelak 2018

The Microbiota has Dwindled and there are Consequenceshellip


How do we Diversify and Restorethe Microbiota

bull Avoid andor limit medical interventions that can cause dysbiosisbull or attenuate the consequences when they must be used

bull Avoid food additives and environmental chemicals that damage the microbiota

bull Avoid andor limit duration of dietary approaches that cause dysbiosisbull or attenuate if there is good evidence for their use in clinical scenario

bull Avoid andor limit use of natural medicines that can cause dysbiosis

bull Prescribe interventions that enhance microbial diversity and nurture the colonic ecosystem


Medications that Induce Dysbiosis Antibiotics

The factor with the greatest detrimental impact on the microbiota (Hawrelak amp Myers 2004) (Jin et al 2016)(Lichtman et al 2016)(Kilkkinen et al 2002)

NB ndash each antibiotic has a different effect on the microbiota

research using culturing techniques suggested quantitative changes could last up to 40 days

alterations in microbiota function can last up to 16 months in adults

long-lasting inflammation

both GIT and systemic



New research using more sensitive molecular analysis techniques (16s rRNA) has revealed (Jernberg et al 2010)(Cotter 2012)

bull alterations can last significantly longer than previously believedbull 18-24 months after a single course of clindamycin

bull 4 years after triple therapy for Helicobacter pylori

bull some organisms never recover

bull localised extinction


From (Francino 2015)


Medications that Induce Dysbiosis Proton Pump

Inhibitorsbull Use of PPIs associated with

bull a marked decline in microbiota diversity (Seto et al 2014)

bull occurs within 7 days of beginning PPI

bull partly reversed 1 month post-administration

bull increased risk of SIBO (Lo amp Chan 2013)

bull increased risk of Clostridium difficile infection (Janarthanan et al 2012)

bull decreased small bowel bifidobacteria concentrations (Wallace et al

2011)

bull significantly lower abundance of total gut bacteria and lower microbial diversity in PPI users (Jackson et al 2016)

bull higher abundance of Proteobacteria and Streptococcus


Medications that Induce Dysbiosis Chemotherapy

bull Chemotherapy (wide range of agents used) (Zwielehner et al 2011)

bull absolute decrease in faecal bacterial concentrations bull specific decreases in populations of bacteroides bifidobacteria and

Clostridium clusters IV (including Faecalibacterium prausnitzii) and XIVa

bull Enterococcus faecium populations increased

bull some patients became colonised with Clostridium difficile


Other Medications to have on the Dysbiosis Radar

bull Recent data suggests the following medications also have the capacity to negatively impact the microbiota (Le Bastard et al 2018)(Makivuokko et al 2010)

bull Metforminbull increases in Proteobacteria

bull E coli Shigella Klebsiella Citrobacter Enterobacter and Salmonella spp

bull decreases in Intestinibacter (a butyrate-producer)bull increases in Akkermansia and Bifidobacterium

bull NSAIDsbull increases in Proteobacteria bull decreases in lactobacilli

bull Atypical antipsychoticsbull significant decrease in overall diversity

bull Statinsbull increases in streptococci and ruminococci

bull Polypharmacy in elderly (Ticinesi et al 2017)

bull the more meds the lower the diversitybull PPIs anti-depressants and anti-psychotics had the most impactbull those with very low microbiota diversity had significant increase in mortality

after a 2-year follow-upcopy Dr Jason Hawrelak 2018

Medical Interventions that Induce Dysbiosis Radiotherapy

bull n=9 gynaecological cancer patients undergoing radiotherapy (Nam et al 2013)

bull 5xwk for 5 wks

bull significant decrease in microbial diversitybull especially amongst the Firmicutes phylum


Food Additives that Induce Dysbiosis Artificial Sweeteners

bull Sucralose consumption (Abou-Donia et al 2008)

bull Causes significant changes in the microbiotabull Reductions in

bull total anaerobes

bull total aerobes

bull specific bacteria

bull bifidobacteria

bull lactobacilli

bull Increased faecal pH



bull Saccharin consumption (Suez et al 2014)

bull Increased populations of bacteroides and staphylococci

bull Decreased concentrations of Lactobacillus reuteri and Akkermansia muciniphila

bull Microbiota changes associated with development of glucose intolerance


Food Additives that Induce Dysbiosis Dietary Emulsifiers

bull Ingestion of dietary levels of emulsifiers carboxymethylcellulose and polysorbate-80(Chassaing et al 2015)

bull Both agents significantly decreasedbull overall microbial diversity

bull increased populations of inflammation-promoting proteobacteria

bull Induction of both low-grade gut inflammation ampmetabolic syndrome


Food Additives that Induce Dysbiosis Environmental Chemicals

bull Roundup (Glyphosate)bull glyphosate-based herbicides are broad-spectrum herbicides that act on

the shikimate pathway in plants but also bacteria and fungi

bull Administered to rats in drinking water at doses comparable to the US Acceptable Daily Intake (ADI) bull from gestational day 6 to postnatal day 125

bull Low-dose exposure to Roundup and glyphosate resulted in significant and distinctive changes in overall bacterial compositionbull no significant changes in the mums but in the next generation

bull at PND 31 (corresponding to pre-pubertal age in humans) relative abundance for Bacteriodetes was increased while the Firmicutes (specifically Lactobacillus spp) was reduced

bull ldquoless stability of the early-life microbiotardquocopy Dr Jason Hawrelak 2018


bullOther environmental chemicals (Hu et al 2016)

bull diethyl phthalate (DEP) methylparaben (MPB) triclosan (TCS)-and their mixture (MIX) were administered at doses comparable to human exposure to rats from birth through adulthoodbull all grps relative abundance for Bacteroidetes was increased while the

relative abundance of Firmicutes was reduced

bull MPB TCS amp MIX = uarr abundance of proteobacteria

bull ldquohellipexposure to the environmental chemicals produced a more profound effect on the gut microbiome in adolescentsrdquo


Dietary Approaches that Induce Dysbiosis

High protein ndash low carb (Duncan et al 2007)

bull Decreases in faecal concentrations of bifidobacteriabull 50 decline on a high-protein + low-carb diet in just 4 weeks

bull Decreases in concentrations of butyrate-producing speciesbull Roseburia spp and Eubacterium rectale

bull Decreases in faecal butyrate



bull Ketogenic dietbull Classic ketogenic diet resulted in a significant increase in

Desulfovibrio spp concentrations (Tagliabue et al 2017)

bull there was no significant impact on other microbial species

bull A very low carbohydrate-high fat diet resulted in a significant reduction in bifidobacteria populations and a decrease in faecal SCFA and butyrate concentrations (Brinkworth et al 2009)

Consider supplementing with prebiotics and

additional fibre (such as psyllium) to attenuate some of these changes



bull Standard Australian Diet (SAD)bull Low in polyphenols

bull Low in total dietary fibre

bull Low in fibre diversity

bull High in processed foods and food additives

bull High exposure to environmental chemicals

bull Low in microbiota-accessible carbohydrates amp polyphenols

bull Western diet starves our microbial selves (Sonnenburg amp

Sonnenburg 2014)


Natural Medicines capable of Inducing Dysbiosis

bull Citrus seed extractbull no tradition of usebull not a natural product

bull appears to be spiked with benzethonium chloride triclosan andormethylparaben (von Woedtke et al 1999)(Takeoka et al 2005)(Avula et al 2007)

bull High-dose amp long-term berberinebull collateral damage with more than 3+ months of continual use

bull Enteric-coated essential oilsbull very potent and concentrated plant extracts bull use tinctures as first line of txtbull try to limit to less than 3 months of continual use

bull Biofilm busting productsbull some are novel formulations with no tradition of usebull no human trials performed to assess microbiota impactbull beneficial microbes live in biofilm too


How can we Protect and Maintain a Healthy Colonic Microbiota

bull Help our patients avoid factors that damage their microbiota

bull dietary advicebull attenuation strategies

bull support microbiota during and after chemotherapy and radiotherapy and necessary antibiotic therapy

bull educate them to avoid unnecessary AB therapy and PPI therapy

bull education on how to minimise food additive and environmental chemical exposure

bull avoid the use of microbiota-harming ldquonaturalrdquo medicinesbull eg citrus seed extract

bull Encourage consumption of a diet and specific supplements and foods that nourish and feed the microbiota


Strategies to Improve Microbiota Diversity

bull Take prebiotic supplements daily

bull Eat a wide diversity of multi-coloured whole plant foods and plant fibres weeklybull resistant starches polyphenols prebiotic-rich foods prebiotic-

like foods gums mucilages pectins soluble and insoluble fibres

bull 40+ different whole minimally-processed plant foods each week

bull Live on a farm andor do lots of organic gardening

bull Eat more raw fruits vegetables nuts and seedscopy Dr Jason Hawrelak 2018

To Improve Microbiota Diversity

bull Exercise moderately

bull Probiotic supplements amp fermented foodsbull will temporarily improve the

diversity

bull can help restore a very damaged ecosystem

bull Faecal Microbial Transplant


Whole Plant Food Diversity = Microbiota Diversity


Strategies to Improve Microbiota Composition

bull Probiotic supplementation

bull Prebiotic supplements

bull Whole plant foods

bull Polyphenol-rich foods

bull Prebiotic-rich foods

bull Prebiotic-like foods

bull Resistant starch-rich foodscopy Dr Jason Hawrelak 2018

Probiotics that Help Restore a Healthy GIT Microbiota

bull Use specific probiotic strains that enhance the growth of your indigenous beneficial bacteria andor decrease potential pathogen populationsbull Bacillus coagulans GBI-30 6086 (Nyangale et al 2015)

bull significant increase in populations of Faecalibacterium prausnitziibull Bifidobacterium lactis HN019 (Ahmed et al 2007)

bull significant increases in faecal concentrations of bifidobacteria lactobacilli and enterococci compared to baseline as well as a decrease in coliforms

bull Bifidobacterium longum BB536 bull significant increase in faecal bifidobacteria concentrations (Kondo et al 2013)

bull significant decrease in enterotoxigenic Bacteroides fragilis populations (Odamaki et al 2012)

bull Lactobacillus acidophilus NCFM (van Zanten et al 2014)

bull significant increase in faecal bifidobacteria lactobacilli and eubacteria bull Lactobacillus casei Shirota (Ishikawa et al 2005)

bull significant increase in faecal bifidobacteria concentrations bull Lactobacillus reuteri DSM 17938 (del Campo et al 2014)

bull significant reductions in proteobacteria populations ndash from 64 of ecosystem to 32bull Lactobacillus rhamnosus GG (Benno et al 1996)

bull significant increases in faecal concentrations of bifidobacteria and lactobacilli as well as decreases in lecithinase-negative clostridia concentrations copy Dr Jason

Hawrelak 2018

Prebiotic Supplements amp their Dosages(Hawrelak 2013)(Cherbut Michel Raison Kravtchenko amp Severine 2003) (Takahashi et al 1994)

bull Acacia fibre bull at least 10gday

bull Lactulose (syrup) bull at least 5mlday

bull GOSbull at least 3gday

bull FOSinulin bull at least 3gday

bull Partially-hydrolysed guar gum bull at least 5gday


Prebiotic Dose Effects on the GIT MicrobiotaFructooligosaccharides 4gday Increase in bifidobacteria decrease in β-glucuronidase activity (Buddington et al 1996)

10gday Increase in bifidobacteria and Faecalibacterium prausnitzii (Ramirez-Farias et al 2009)

15gday Increase in bifidobacteria decrease in faecal bacteroides clostridia and fusobacteria concentrations

(Gibson et al 1995)

40gday Increase in bifidobacteria decrease in faecal concentrations of enterococci and enterobacteria (Kleesen

et al 1997)

Galactooligosaccharides 25gday Increase in bifidobacteria decrease in faecal concentrations of protein putrefactive byproducts (indoles

and isovaleric acid) (Ito et al 1993)

26gday Faecal bifidobacteria counts increased significantly as did faecal levels of Lactobacillus-Enterococcus

spp Concentrations of Bacteroides spp the Clostridium histolyticum group E coli and Desulfovibrio

spp decreased compared with placebo treatment (Vulevic et al 2008)

5gday Increase in bifidobacteria and Faecalibacterium prausnitzii decrease in Bacteroides spp (Davis et al 2011)

Lactulose 3 gday The faecal concentration of bifidobacteria increased significantly after treatment whereas the number

of Bacteroidaceae and clostridia decreased Faecal concentrations of protein putrefactive byproducts

(skatol indole and phenols) were reduced with lactulose intake Faecal beta-glucuronidase

azoreductase and nitroreductase activities also decreased Mean faecal pH also dropped from 70 to 64

(Terada et al 1992)

5g twice daily After ingestion faecal populations of bifidobacteria increased (Bouhnik et al 2004)

10g twice

daily

After treatment populations of bifidobacteria and lactobacilli increased by 30 and 19 log units

respectively Populations of Bacteroides Clostridium and coliforms decreased by 41 23 and 18 log

units respectively Mean faecal pH also dropped from 69 to 58 (Ballongue et al 1997)

Partially-hydrolysed guar

gum

6gday Enhanced growth of bifidobacteria as well as butyrate producing bacteria in the Roseburia Eubacterium

rectale group Eubacterium halli and the microbe SS21 (Ohashi et al 2015)

The Better Researched Prebiotics and theirImpact on the Colonic Microbiota

Whole Plant Foods(Tuohy et al 2012)

bull Whole-food minimally processed predominantly plant-based diet

bull moderate fatbull moderate proteinbull rich in varietybull rich in fibrebull rich in colour

bull Whole grains bull Whole grain ricebull Millet buckwheatbull Oats and rye (if gluten is tolerated)

bull Legumes

bull Fruits

bull Vegetables

bull Nuts copy Dr Jason Hawrelak 2018

Polyphenol-Rich Foods(Perez-Jimenez et al 2010)(Min et al 2011)(Leja et al 2013)(Ramdath et al 2014)

bull Fruitsbull Black elderberries black currants blueberries

bull Cherries strawberries blackberries plums raspberries apples (red) black grapes

bull Nuts and Seedsbull Flaxseed meal chestnuts hazelnuts pecans black

tahini


Polyphenol-Rich Foods(Perez-Jimenez et al 2010)(Min et al 2011)(Leja M et al 2013)(Ramdath et al 2014)

bull Vegetablesbull Purple carrots red carrots purplered potatoes red

cabbage spinach red onions broccolicarrots (orange) red lettuce

bull Grainsbull Red rice black rice red and black quinoa whole grain

rye bread (sourdough)

bull Other bull Black olives amp olive oil


Prebiotic-Rich Foods(Hawrelak 2013)(Biesiekierski et al 2011)(Muir et al 2009)(Kuo et al 1988)

bull Consume foods rich in oligofructose inulin (FOS) and galactooligosaccharides (GOS)

bull FOS

bull minimum of 3gday from food sources to achieve a prebiotic effect

bull GOS



Foodstuff Form Average percentage of

FOS fresh weight

Typical Serving Size Approximate

Dose of FOS

per ServeAsparagus raw 25 frac12 bunch (~250g) 63g

boiled 17 frac12 bunch (~250g) 43g

Banana raw 05 Medium sized banana 06gBarley cooked kernels 015 1 cup 02gBurdock (gobo) root (raw) 145 1 cup chopped 180gChicory roasted (as lsquocoffeersquo) 417 1 teaspoon powder 13g

Dandelion leaves (raw) 135 frac12 cup chopped 20g

root (raw) 79 1 cup chopped 80g

Garlic raw 129 1 medium-sized clove 04gGlobe artichoke boiled 44 1 medium-sized bud

(assuming 45 edible

portion)

30g

Jerusalem

artichoke

tubers (raw) 180 Medium tuber 90g

Leek raw 30 1 cup chopped 27gOnion raw 43 frac12 cup chopped 35g

cooked 31 frac12 medium-sized onion 30g

Rye flour (raw) 07 1 cup 09gSalsify root (raw) 42 1 cup chopped 43gWheat flour (baked) 24 1 cup 29gYacon root (raw) 110 1 cup chopped 132g

List of FOS-containing foods (Hawrelak 2013)copy Dr Jason Hawrelak 2018

Fructooligosaccharides (FOS)

Galactooligosaccharides (GOS)

Foodstuff Form Average percentage

of GOS fresh weight

Typical Serving Size Dose of GOS

per ServeBeetroot tuber (raw) 014 1 cup grated 020g

Borlotti beans canned 100 frac12 cup 091g

Broccoli raw 013 frac12 cup chopped 005g

Chick peas boiled 125 frac12 cup 108g

Fennel Bulb (raw) 010 1 cup sliced 009g

Haricot beans boiled 109 frac12 cup 109g

Lentils - green boiled 046 frac12 cup 043g

Lentils - red boiled 046 frac12 cup 043g

Lima beans boiled 134 frac12 cup 122g

LSA Mix raw and ground 058 1 tablespoon 007g

Oats dry 034 frac12 cup 012g

Onion raw 019 frac12 medium onion 011g

Radicchio raw 011 1 cup chopped 006g

Red kidney beans boiled 144 frac12 cup 133g

Ryebread sourdough 033 2 slices 017g

Soy beans boiled 079 frac12 cup 067g

Split peas boiled 188 frac12 cup 170g

Wheat (wholemeal) bread 05 2 slices 024g

List of GOS-containing foods (Muir et al 2009)(Biesiekierski et al 2011)


Prebiotic-like Foods

bull Brown rice (Benno et al 1989)

bull Carrots (Tamura 1983)

bull Black currants (Molan et al 2014)



bull Dark cocoa (Tzounis et al 2011)

bull Almonds (Liu et al 2014)

bull Green tea (Goto et al 1998)


Resistant Starch-Rich Foods

bullRS1bull found in grains seeds and legumes

bull resists digestion because the starch is trapped within the cellulose cell walls (physically inaccessible)

bull if finely milled rarr less RS content

bull cooked oats vs soaked oats

bull Richer sourcesbull Buckwheat sorghum


The 4 Different type of Resistant Starch

bullRS2bull starch with a high amylose content

bull not easily broken down by our digestive enzymes

bull is found in some starchy foods including raw potatoes plantains and green (unripe) bananas

bull also in legumes

bull cooking these foods makes the starch digestible

bull the predominant form found in dietary supplements amp functional foods

bull found in plantain flour green banana flour and potato starchbull these must be eaten unheated



bull RS3bull formed when certain starchy foods including root vegetables and whole grains are cooked and then cooledbull termed retrograde starchbull cooling process turns some of the digestible starches into resistant starches (via retrogradation)bull also found in legumes

bull black beans adzuki beans red lentils chick peas kidney beans peas (dried) faba beans

bullRS4bull human-made via a chemical process


We are the Custodians of the Microbiota

bull It is important to protect the microbiota when we can and restore it when the damage has already been done

bull Massive loss of diversity in Westerners (Schnorr et al 2014)

bull Hadza vs healthy Westernbull 3 generations of antibioticsbull Widespread use of NSAIDs and PPIsbull Western dietbull C-section births formula feeding anti-bacterial everything

bull What we do to our microbiota can impact our entire lineage (Blaser amp Falkow 2009)

bull We can only pass on the microbiota that we have



We do not inherit the earth

from our ancestors we borrow it from our children

We do not inherit the

microbiota from our ancestors we borrow it

from our children


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diversity of the gut microbiota in infants with atopic eczema J Allergy Clin Immunol 129(2) 434-440 440 e431-432

bull Abrahamsson T R H E Jakobsson A F Andersson B Bjorksten L Engstrand and M C Jenmalm (2014) Low gut microbiota diversity in early infancy precedes asthma at school age Clin Exp Allergy 44(6) 842-850

bull Alisi A Ceccarelli S Panera N amp Nobili V (2012) Causative role of gut microbiota in non-alcoholic fatty liver disease pathogenesis Frontiers in Cellular and Infection Microbiology 2 132 doi103389fcimb201200132

bull Anhe F F G Pilon D Roy Y Desjardins E Levy and A Marette (2016) Triggering Akkermansia with dietary polyphenols A new weapon to combat the metabolic syndrome Gut Microbes 7(2) 146-153

bull Attaluri A M Jackson J Valestin and S S Rao (2010) Methanogenic flora is associated with altered colonic transit but not stool characteristics in constipation without IBS Am J Gastroenterol 105(6) 1407-1411

bull Attene-Ramos M S E D Wagner M J Plewa and H R Gaskins (2006) Evidence That Hydrogen Sulfide Is a Genotoxic Agent Molecular Cancer Research 4(1) 9-14

bull Bajaj J S P M Gillevet N R Patel V Ahluwalia J M Ridlon B Kettenmann C M Schubert M Sikaroodi D M Heuman M M Crossey D E Bell P B Hylemon P P Fatouros and S D Taylor-Robinson (2012) A longitudinal systems biology analysis of lactulose withdrawal in hepatic encephalopathy Metab Brain Dis 27(2) 205-215

bull Ballongue J (1998) Bifidobacteria and probiotic action Lactic Acid Bacteria Microbiology and Functional Aspects S Salminen and A von Wright New York Marcel Dekker 2nd 519-587

bull Ballongue J C Schumann and P Quignon (1997) Effects of lactulose and lactitol on colonic microflora and enzymatic activity Scandinavian Journal of Gastroenterology 1997 (suppl 222) 41-44

bull Barnich N J Denizot and A Darfeuille-Michaud (2013) E coli-mediated gut inflammation in genetically predisposed Crohns disease patients Pathol Biol (Paris) 61(5) e65-69

bull Bentley R and R Meganathan (1982) Biosynthesis of vitamin K (menaquinone) in bacteria Microbiol Rev 46(3) 241-280


bull Berni Canani R Di Costanzo M amp Leone L (2012) The epigenetic effects of butyrate potential therapeutic implications for clinical practice Clinical Epigenetics 4(1) 4 doi1011861868-7083-4-4

bull Blaser M J amp Falkow S (2009) What are the consequences of the disappearing human microbiota Nat Rev Micro 7(12) 887-894

bull Blaser M J (2017) The theory of disappearing microbiota and the epidemics of chronic diseases Nature Reviews Immunology 17 461 doi101038nri201777

bull Blaut M and T Clavel (2007) Metabolic Diversity of the Intestinal Microbiota Implications for Health and Disease The Journal of Nutrition137(3) 751S-755S

bull Bouhnik Y S Alain A Attar B Flourie L Raskine M J Sanson-Le Pors and J C Rambaud (1999) Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome Am J Gastroenterol 94(5) 1327-1331

bull Bouhnik Y Attar A Joly FA Riottot M Dyard F Flourie B Lactulose ingestion increases faecal bifidobacterial counts A randomised double-blind study in healthy humans Eur J Clin Nutr 200458(3)462-6

bull Bourassa M W Alim I Bultman S J amp Ratan R R (2016) Butyrate neuroepigenetics and the gut microbiome Can a high fiber diet improve brain health Neuroscience Letters 625 56-63 doihttpdxdoiorg101016jneulet201602009

bull Brahe L K E Le Chatelier E Prifti N Pons S Kennedy T Hansen O Pedersen A Astrup S D Ehrlich and L H Larsen (2015) Specific gut microbiota features and metabolic markers in postmenopausal women with obesity Nutrition amp Diabetes 5 e159

bull Brinkworth GD Noakes M Clifton PM Bird AR Comparative effects of very low-carbohydrate high-fat and high-carbohydrate low-fat weight-loss diets on bowel habit and faecal short-chain fatty acids and bacterial populations Br J Nutr 2009101(10)1493-502

bull Buddington RK Williams CH Chen S et al Dietary supplement of neosugar alters the fecal flora and decreases activities of some reductive enzymes in human subjects American Journal of Clinical Nutrition 199663709-16

bull Buts J-P P Bernasconi J-P Vaerman and C Dive (1990) Stimulation of secretory IgA and secretory component of immunoglobulins in small intestine of rats treated withSaccharomyces boulardii Digestive Diseases and Sciences 35(2) 251-256

bull Caesar R V Tremaroli P Kovatcheva-Datchary Patrice D Cani and F Baumlckhed (2015) Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling Cell Metabolism 22(4) 658-668

bull Canani R B M D Costanzo L Leone M Pedata R Meli and A Calignano (2011) Potential beneficial effects of butyrate in intestinal and extraintestinal diseases World J Gastroenterol 17(12) 1519-1528

bull Cani P D J Amar M A Iglesias M Poggi C Knauf D Bastelica A M Neyrinck F Fava K M Tuohy C Chabo A Waget E Delmee B Cousin T Sulpice B Chamontin J Ferrieres J F Tanti G R Gibson L Casteilla N M Delzenne M C Alessi and R Burcelin (2007) Metabolic endotoxemia initiates obesity and insulin resistance Diabetes 56(7) 1761-1772

bull Chang D-E Jung H-C Rhee J-S et al Homofermentative Production of d- or l-Lactate in Metabolically Engineered Escherichia coli RR1 Applied and Environmental Microbiology 199965(4)1384-89

bull Charalambous B M Stephens R C Feavers I M amp Montgomery H E (2007) Role of bacterial endotoxin in chronic heart failure the gut of the matter Shock 28(1) 15-23 doi101097shk0b013e318033ebc5

bull Chen H L Cheng H C Wu W T Liu Y J amp Liu S Y (2008) Supplementation of konjac glucomannan into a low-fiber Chinese diet promoted bowel movement and improved colonic ecology in constipated adults a placebo-controlled diet-controlled trial J Am Coll Nutr 27(1) 102-108

bull Cryan J F amp Dinan T G (2012) Mind-altering microorganisms the impact of the gut microbiota on brain and behaviour Nat Rev Neurosci 13(10) 701-712

bull Dao M C A Everard J Aron-Wisnewsky N Sokolovska E Prifti E O Verger B D Kayser F Levenez J Chilloux L Hoyles M-O Consortium M-E Dumas S W Rizkalla J Doreacute P D Cani and K Cleacutement (2015) Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity relationship with gut microbiome richness and ecology Gut

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bull Wu G D J Chen C Hoffmann K Bittinger Y Y Chen S A Keilbaugh M Bewtra D Knights W A Walters R Knight R Sinha E Gilroy K Gupta R Baldassano L Nessel H Li F D Bushman and J D Lewis (2011) Linking long-term dietary patterns with gut microbial enterotypes Science 334(6052) 105-108

bull Yurkovetskiy L Pickard J M amp Chervonsky A V (2015) Microbiota and Autoimmunity exploring new avenues Cell Host amp Microbe 17(5) 548-552 doi101016jchom201504010

bull Zhou D Pan Q Xin F Z Zhang R N He C X Chen G Y Fan J G (2017) Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier World J Gastroenterol 23(1) 60-75 doi103748wjgv23i160

bull Zhu L S S Baker C Gill W Liu R Alkhouri R D Baker and S R Gill (2013) Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients A connection between endogenous alcohol and NASH Hepatology 57(2) 601-609

bull Zwielehner J C Lassl B Hippe A Pointner O J Switzeny M Remely E Kitzweger R Ruckser and A G Haslberger (2011) Changes in human fecal microbiota due to chemotherapy analyzed by TaqMan-PCR 454 sequencing and PCR-DGGE fingerprinting PLoS One 6(12) e28654


AKA the microflora or GIT ecosystem

Human gut microbiota contains 1014 living microorganisms (Neish 2009)(Lozupone 2012)

bull this may be 10 times the number of cells in the human bodybull from over 1000 different species

bull a mutually beneficial symbiotic relationshipbull a collection of cells that work in unison with the host and that can

promote health but sometimes initiates disease

bull dysbiosis

















development





bull vitamin K






Anxiety

Asthma

Atopic eczema

Autism


Depression

Kidney stones

Metabolic syndrome

Multiple sclerosis

Obesity



Type I diabetes

Type II diabetes





Coeliac disease

Crohnrsquos disease



Liver cirrhosis



SIBO


GIT Microbiota


amp Knight 2012)











bull obesity



bull auto-immunity














From (Blaser 2017)







bull AB cocktails

















































2011)
























bull 5xwk for 5 wks







bull total aerobes


bull bifidobacteria

bull lactobacilli



















































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children






















































































































































































development





bull vitamin K






Anxiety

Asthma

Atopic eczema

Autism


Depression

Kidney stones

Metabolic syndrome

Multiple sclerosis

Obesity



Type I diabetes

Type II diabetes





Coeliac disease

Crohnrsquos disease



Liver cirrhosis



SIBO


GIT Microbiota


amp Knight 2012)











bull obesity



bull auto-immunity














From (Blaser 2017)







bull AB cocktails

















































2011)
























bull 5xwk for 5 wks







bull total aerobes


bull bifidobacteria

bull lactobacilli



















































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children









































































































































































Anxiety

Asthma

Atopic eczema

Autism


Depression

Kidney stones

Metabolic syndrome

Multiple sclerosis

Obesity



Type I diabetes

Type II diabetes





Coeliac disease

Crohnrsquos disease



Liver cirrhosis



SIBO


GIT Microbiota


amp Knight 2012)











bull obesity



bull auto-immunity














From (Blaser 2017)







bull AB cocktails

















































2011)
























bull 5xwk for 5 wks







bull total aerobes


bull bifidobacteria

bull lactobacilli



















































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children







































































































































































GIT Microbiota


amp Knight 2012)











bull obesity



bull auto-immunity














From (Blaser 2017)







bull AB cocktails

















































2011)
























bull 5xwk for 5 wks







bull total aerobes


bull bifidobacteria

bull lactobacilli



















































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children












































































































































































bull obesity



bull auto-immunity














From (Blaser 2017)







bull AB cocktails

















































2011)
























bull 5xwk for 5 wks







bull total aerobes


bull bifidobacteria

bull lactobacilli



















































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children



















































































































































































From (Blaser 2017)







bull AB cocktails

















































2011)
























bull 5xwk for 5 wks







bull total aerobes


bull bifidobacteria

bull lactobacilli



















































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children












































































































































































bull AB cocktails

















































2011)
























bull 5xwk for 5 wks







bull total aerobes


bull bifidobacteria

bull lactobacilli



















































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children














































































































































































































2011)
























bull 5xwk for 5 wks







bull total aerobes


bull bifidobacteria

bull lactobacilli



















































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children



























































































































































































bull 5xwk for 5 wks







bull total aerobes


bull bifidobacteria

bull lactobacilli



















































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children











































































































































































bull total aerobes


bull bifidobacteria

bull lactobacilli



















































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children























































































































































































































Sonnenburg 2014)




























diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children

































































































































































































diversity

























Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children




























































































































































































Hawrelak 2018











(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children

















































































































































































(Gibson et al 1995)


et al 1997)











(Terada et al 1992)


10g twice

daily





gum








bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children











































































































































































bull Legumes

bull Fruits

bull Vegetables






tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children











































































































































































tahini











bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children
















































































































































































bull FOS


bull GOS




FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children








































































































































































FOS fresh weight


Dose of FOS







(assuming 45 edible

portion)

30g

Jerusalem

artichoke









of GOS fresh weight

































































from our children









































































































































































of GOS fresh weight

































































from our children


















































































































































































































from our children







































































































































































how to diversify a dwindling microbiome to... · 2018-06-15 · how to diversify a dwindling...

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