probiotics final 2
TRANSCRIPT
THE Annual probiotic symposium
The Yakult India Microbiota and Probiotic Science Foundation
3rd and 4th December 2016 Chennai -INDIA
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MUGH MUGH
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LEBANON
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Role of Probiotics in GI DISEASES”
Asso. Prof. Dr Aziz koleilatBeirut Arab University
Makassed University General HospitalBeirut –Lebanon
Makassed @[email protected]
PASPGHAN PASPGHAN
• Definition & history…. • Characteristics & properties.• Functions & action. • Clinical application in
gastroenterology
• Misconcepts • Dosage • Disadvantage & Safety.
• Conclusion.
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MUGH
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THE EQQUILIBRIUM OF NATURE
THE EQUILIBRIUM OF HUMAN BODY
THE EQUILIBRIUM OF THE GUT FLORA
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Definition
Probiotics Live microorganisms that confer a health benefit on the host when administered in adequate amounts.
Prebiotic Dietary substances that nurture specific changes in the composition and/or activity of the GI microbiota (favoring beneficial bacteria), thus conferring benefit(s) upon host health.
Synbiotics Products that contain both probiotics and prebiotics.
(Fuller, 1989 ,Roberfroid 2000,Gibson et al. 200).
Adapted from Guarner F, Khan AG, Garisch J, et al. Probiotics and prebioticsworld gastroenterology organisation global guidelines, 2011.
Louis Pasteur
(1822 - 1895)
Metchnikoff Elie
(1848-1916)
Potential benefits of Lactobacillus~125 yrs ago 1905: Concept of Probiotics
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Tissier , In 1899
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Fuller ,1989, defined probiotics as microbial supplements that benefit the host animal by improving its intestinal microbial balance*.
Strachan, in 1989 propagated The hygiene hypothesis.
*Martin H. Floch et al , 2001 , Nutrition
Parker, In1974 was actually the first to use the term "probiotic." in the clinical sense in which it is now employed.*
Gibson and Roberfroid ,in 1995 introduced the concept of prebiotics. J Nutr 1995, 125: 1401-1412.
Isoulori ….in 1999 introduced Probiotics concept as immunomodulators. (AAA&I).
*Martin H. Floch et al , 2001 , Nutrition .**IMF (Infant Milk Formula)
Probiotics
New England Journal of Medicine 2002
Not all probiotics have same effect or functionThey are strain specific – with specific mechanism …..• Can be used in combination Or each alone…..
Lactobacillus bacteria mainly in the small intestine.Bifidobacteria reside in the large intestine.
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Now, Genetically engineered species that secrete immunomodulators ex.Lactococcus lactis
Probiotics
The MAPK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.
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Function and Action of PROBIOTICS Modulate intestinal
immune function•Reduce pro inflammatory cytokines•Promote telarogenic cytokines profile•Increase secretory IgA
Promote epithelial cell hemostasis
•Enhance barrier function•Promote cyto protective responses•Improve cell survival•Increase mucin production
Neuromodulatory effects •Muco-opioid and canaobiod receptors on epithelial cells •Reduces visceral hypersensitivity and stress responses via enteric nerve cells.
Block effect of pathogens •Reduce pathogens binding•Decrease luminal PH•Produce anti bacterial bacitrocin
Nutritional benefit • Assist in breakdown of un digestable food to produce usable nutrient
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Probiotics communication with a variety of cell types In the GI tract
Ann Gastroenterol. 2015
How Probiotics Work
Lumen
(Adapted )Fedorak RN and Madsen KL Inflamm Bowel Dis, 2004Cristiano Pagnini et al PNAS 2010 107:454-459; adapted
lamina propria
Enhanced barrier integrity
Anti microbial activitySecretesbacitreocin,defensins
Stimulation of an immune response
---Increase IgA
Immunomodulatory action Decrease TNF & INFג
secretion Increase TGFβ &IL10
secretion Induce T reg cell Induce T cell apoptosis Dendretic cell modulation
•Competitive exclusion of bacteria (Translocation & adhesion)
Nuclear factor-κB (NF-κB)
Dendretic cells.cell
PROBIOTICS
Enhanced tight junction
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Different Actions of Probiotics Action SpeciesProduce pathogen- inhibitory substances L. reuteri
L. rhamnosus GG
Inhibit pathogen attachment S. boulardii & L. acidophilus B.clausii
Inhibit the action of microbial toxins S. boulardii
Stimulate immunoglobulin A S. boulardii L. rhamnosus GG
Trophic effects on intestinal mucosa
S. boulardii
Gary W. Elmer Am J Health-Syst Pharm 2001Expert Review Gastroenterology &Hepatology 2016
Prevention of barrier gut impairment B clausi
. Luminal Conversion and
Immunoregulation by ProbioticsFront. Pharmacol., 2015 Bahanu et al
Probiotic influence on different immune functions Immune system effect Organism
Increased phagocytosis capacity
L. acidophilus (johnsonii) La1L. casei B. lactis Bb12B. lactis HN019 L. rhamnosus GG L. rhamnosus HN0
Increased NK cell activity L. Rhamnosus HN001
B. lactis HN109 L. casei subsp. casei + dextran
Stimulation of IgA production
• B. bifidum• L. acidophilus (johnsonii)• La1L. casei rhamnosus GG• B. lactis Bb12
Suppression of lymphocyte proliferation Induction of apoptosis
L. rhamnosus GG L. casei GG B. lactis L. Acidophilus L. delbrueckii subsp.
bulgaricu S. thermophilus L. paracasei E. coli Nissle 1917
Increased cell- mediated immunity
L. casei Shirota
V. Delcenserie 2008 curr,Issues Mol Chennai 2016 (Loris R 2016 Expert Review G&H.)
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What is new
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Probiotics Improve NAFLD in Obese Children and Adolescents
Famouri, Fatemeh; Shariat, Zainab; Hashemipour, Mahin; Keikha, Mojtaba; Kelishadi, RoyaJournal of Pediatric Gastroenterology and Nutrition November 03, 2016
A probiotic compound containing Lactobacillus acidophilus, Bifidobacterium lactis, B. bifidum, and L. rhamnosus was found to be effective in reducing biochemical and sonographic features of NAFLD in obese children.
Non-alcoholic fatty liver disease (NAFLD)
• There was a significant decrease seen in serum alanine aminotransferase and aspartate aminotransferase, as well as a decline in mean cholesterol, LDL-C, and triglycerides
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Probiotic and Synbiotic Therapy in Critical IllnessWilliam Manzanares; Margot Lemieux; Pascal L. Langlois; Paul E. Wischmeyer
Crit Care. 2016;20(262)
o Critical illness is characterized by a loss of commensal flora and an overgrowth of potentially pathogenic bacteria, leading to a high susceptibility to nosocomial infections
Probiotics significantly reduced the incidence of infectious complications, including new episodes of VAP(Ventilator-associated pneumonia )in critically ill patients.
o In the largest systematic review and meta-analysis of probiotics to date, in 30 trials enrolling 2972 patients
Probiotics protect the gut barrier, attenuate pathogen overgrowth, decrease bacterial translocation and prevent the infection.
Probiotic therapy with L. plantarum currently demonstrates the most significant effect on the reduction of infections..
(Klarin 2005 McNaught 2005 Klarin 2008) *(William Manzanares 2016)
Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Rousseaux C, Thuru X, Gelot A et al.Nat Med 2007;13:35–37.
Abstract• Abdominal pain is common in the general population and, in
patients with irritable bowel syndrome, is attributed to visceral hypersensitivity.
• Oral administration of specific Lactobacillus strains induced the expression of mu-opioid and cannabinoid receptors in intestinal epithelial cells, and mediated analgesic functions in the gut-similar to the effects of morphine.
Rousseaux C. Nat Med.2007David B 2016 . Chennai 2016
These results suggest; That the microbiology of the intestinal tract influences
our visceral perception, That new approaches for the treatment of abdominal
pain and irritable bowel syndrome. (Marilla Carabotti et al 2015)
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Marilla Carabotti et al (2015) Ann Gastroenterol. Apr-Jun; 28(2): 203–209 Mary Sanders (2010)Academy of science new yorkKoleilat (2016) EC Pediatrics 2.4:190-200
The gut-brain axis: interactions between enteric microbiota,
central and enteric nervous systems Annals of Gastroenterology (2015) 28, 1-7
Marilia Carabottia, Annunziata Sciroccoa, Maria Antonietta Masellib, Carola Severia University Sapienza, Rome; S. De Bellis, Castellana Grotte, Bari, Italy
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The balance of probiotic
Clinical application of probioticsin gastroenterology
Potential applications of probiotics for prevention and/or treatment of a large number of gastrointestinal disorders, including: in use already. Rota associated diarhea( Vanderhoof, J Pediatr 1999; (G Grandy 2010 BMC ,Marteau
PR, de Vrese M, Cellier CJ, Schrezenmeir JAm J Clin Nutr. 2001)
Antibiotic-associated diarrhea, (Szajewska ET al.JPGN 2001; Fang Yan cur opn 2010)
Infantile diarrhea. (Guandalini et al., JPGN, 2000)
IBD, (Rahimi R Dis Sci 2008,Pronio inf Bowel dis 2008)
IBS,(Quigly Jclin gast2008,HovevdaBMC2009)
Neonatal necrotizing enterocolitis (NEC),(CaplanJ Pein.2009)
Enteropathy in HIV infection, (MartinezCan J Micro 2009)
Fang Yan; David Brent Polk; Probiotics: progress toward novel therapies for intestinal diseasesCurr Opin Gastroenterol. 2010;26(2):95-101.
By down regulation amiloration , adjuvents, or synergisim
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Diseases that have been reportedly treated with probiotics include:
Allergy ,atopic Eczema (Isoulori 201
Obesity (Sean Davies et al , the Journal of Clinical Investigation, 24 June 2014
Intestinal pain (Rousseaux C .Nat Med.2007 )
Gluten intolerance, gastroenteritis, (Smecuol E 2013)
Helicobacter pylori infection, (Lesbros-Pantoflickova - 2007j.n) (Loris R 2016 Expert Review G&H.)
Colon cancer.(abdekrazak Arch Pediatr Adolesc Med. 2012,2013)
Clinical application of probioticsIn gastroenterology
By: Inflammation degradation ,Immune boosting.
KOLEILAT. Probiotics Nowadays EC Paediatrics2.1(2016):100-107
Proposed use of probiotics in gastroenterology
Radiation induced diarrhea .(P.Delia,et al ,Use of probiotics for prevention of radiation-induced diarrhea World J Gastroenterol. 2007)
Constipation . (Dimidi E ,Christodoulides et al The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2014 )
Infantile colic. (E bennett 2014 bmj probiotics and infant colics )
Dental Caries and Periodontal Disease .(Amit Bhardwaj, Shalu V Bhardwaj Role of Probiotics in Dental Caries and Periodontal Disease Arch Clin Exp Surg. 2012)
Cardiovascular diseases .(RajivSaini, et al 2010 J Cardiovasc Dis : potential of probiotics in controlling cardio vascular diseases )
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The communication of probiotics
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Gastroenterology & probioticsEffect and feasibility
Disease
•Infectious diarrhea•Antibiotic associated diarrhea•C difficile diarrhea•NEC•IBD•IBS•Food allergy•Panceriatitis•Lactose intolerance
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Use of Probiotics for Management of Acute Gastroenteritis:
A Position Paper by the ESPGHAN Working Group for Probiotics and Prebiotics
Hania Szajewska, on Behalf of the ESPGHAN Working Group for Probiotics and
Prebiotics
January 2014 - Volume 58 - Issue 1
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…
General Comments
• Adjunct to rehydration therapy reduced the duration of diarrhea
• Strain specific In efficacy and safety .
• The safety and clinical effects should not be generalized….
• A lack of evidence regarding the efficacy of a certain probiotic(s) does not mean that future
studies will not establish health benefits.
• The efficacy has to be confirmed in well-conducted RCTs,*
*RCT-Randommised clinical trial
The efficacy of specific strains at a specific dosage in a
specific setting are not sufficient evidence to support the
presence of health effects at a lower dosage and in a
different setting.
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. Probiotics in gastrointestinal disorders
The precise mechanism's of action of probiotics has not thus far been clarified.
o Potential mechanisms to consider include: Modulation of GI immunity by:
altering inflammatory cytokine profiles down regulating pro inflammatory cascades inducing regulatory mechanisms in a strain-specific manner;
Inhibiting pathogenic bacterial adherence; Acidification of the colon by nutrient fermentation; Enhancement of epithelial barrier function; Induction of opioid and cannabinoid receptors in intestinal epithelial cells; Reduction of visceral hypersensitivity, spinal afferent traffic, and stress
response (Elizabeth C. 2010,Rousseaux C..2007 ) . Elizabeth C. Et a lTherap Adv، Gastroenterol.2010
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Action of Probiotics in gastrointestinal disorders • Probiotics have intestinal barrier, immunologic, antibacterial, and motility
and sensation effects that may contribute to their efficacy in various indications (Ohland CL2010 )
Have direct effects affect the intestinal mucosa &epithelial barrier by: Increasing mucin expression/secretion by goblet cells . Augmenting production of antimicrobial peptides, including β-defensin; Enhancing tight junction stability decreasing epithelial permeability to
intraluminal pathogens and toxins. (Ohland CL2010 )
Influence mucosal immunity by : Increasing levels of IgA-producing cells in the lamina propria Promoting secretion of secretory IgA into the luminal mucus layers, limit epithelial colonization by bacteria.
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Action of Probiotics in gastrointestinal disorders
Influence cytokine expression and suppress mucosal inflammation, potentially through Toll-like receptor signaling (deRoock 2010).
Attenuate post infectious intestinal dysmotility (, Lactobacillus paracasei (VerduEF 2004)
Prevent and reverse dysmotility associated with intestinal infection. (Collins et al. 2009)
Alleviate visceral hypersensitivity (KamiyaT 2006 ), by induction of expression of cannabinoid and opioid receptors on intestinal cells .
Toll-like receptor
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• Recommendations for Probiotic Use in Humans
• Martin H. Floch, MD* and W. Allan Walker, MDw
J Clin Gastroenterol. 2015 Nov-Dec;49 Suppl 1:S69-73.
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J Clin Gastroenterol. 2011 Nov;45 Suppl:S168-71. doi: 10.1097/MCG.0b013e318230928b.
Recommendations for probiotic use-2011 update.Floch MH1, Walker WA, Madsen K, Sanders ME, Macfarlane GT, Flint HJ, Dieleman LA,
Ringel Y, Guandalini S, Kelly CP, Brandt LJ
The use of probiotics and ingestion of expressed maternal breast milk containing probiotics can help to stabilize colonization and to reduce the incidence and severity of NEC when given to premature infants at risk. (Floch,Walker 2011)
Recommendations for Probiotic Use in Humans—A 2014 Update Necrotizing Enterocolitis
•Bifidobacterium breve BBG-001 failed to prevent NEC in very preterm infant • kate Costeloe et al , Lancet 2016 Feb 28;387(10019):649-60. Epub 2015 Dec 28. Daniells 2015)
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Recommendations for Probiotic Use in Humans—A 2014 Update
Childhood Diarrhea The microbiota is maintained in a stable ecology, and it appears that
probiotics are very helpful in shortening the course of acute gastroenteritis diarrhea [Szujewsku H.2007. Guandalini S. 2008].
• There are numerous studies to establish this.
Reduction of diarrhea duration of little more than 1 day, and to be exerted mostly on diarrhea due to rotavirus.
The effect is strain-dependent, and dose-dependent, with doses of at least 10 billion/d being necessary.
It is clear that starting Saccharomyces boulardii, LGG, or strains of Lactobacillus reuteri are extremely helpful in shortening the course of the diarrhea [Szujewsku H.2007. Guandalini S. 2008].
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Recommendations for Probiotic Use in Humans—A 2014 Update Antibiotic-associated Diarrhea
Probiotics are helpful in the prevention of C. difficile- associated diarrhea in both adults and children. [Goldenberg 2013, Cochrane Database ] .
FMT will be used used for the cure and prevention of resistant C. difficile diarrhea in the coming years.
66% lower infection rate when they received prophylactic probiotics with multispecies probiotics products ,with single-species products reduced the risk by 50%. Johnston 2012
The development of fecal microbial transplantation (FMT) proved that it can cure and prevent resistant C. difficile infection . (Garborg K. 2010,Floch 2012,Hamilton 2012)
S. boulardii, LGG, in combinations [Floch 2011] are helpful in accomplishing this outcome in antibiotic-associated diarrhea
Recommendations for Probiotic Use in Humans—A 2014 Update
Inflammatory Bowel Disease • Pouchitis can be prevented, and remission can be maintained with the use of the probiotic VSL#3[Mimura T.2004].
Therapy reports , ProbioticsVSL#3( Escherichia coli Nissle, S. boulardii and LGG; )was most successful [Miele E.2009).
• Regulate dysbiosis that occurs in simple ulcerative colitis [Floch 2012].
• Dysbiosis, which is seen with C. difficile, can be corrected in selective ulcerative colitis patients and reduce symptom control By FMT [Brace C.2014]
This is the same dysbiosis that is treated with FMT.
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Feacal transplant
VSL#3 was the most effective in ulcerative colitis,
less of an effect in Crohn’s disease which does not respond as well [Shen J., 2014].
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Feacal transplant !!!!!!• FMT permits the administration of over 500 strains of human organisms.
• They certainly fit the definition of a probiotic in that they are human organisms administered to benefit health.(Floch 2012)
• There are many papers in the literature that demonstrate a probiotic —namely, VLS#3—which is effective in ulcerative colitis, pouchitis, and Irritable Bowel Syndrome.(Guandalinni S 2010)
It enables total biological stimulation of the immune system and seeding of the host basic flora for fermentation use, and possibly contains selective
therapeutic inhibition substances such as defensins.
Koleilat : Fecal microbiota transplantation Review CRNSS Update series october 2016:1-9
Recommendations for Probiotic Use in Humans—A 2014 Update
Irritable Bowel Syndrome (IBS) • IBS is a major international clinical problem. Bifidobacterium infantis B5624 (Ireland) has given the best reports for
relief of symptoms ” with good rating [Groeger D., 2013]. – Lactobacillus plantarum and Bifidobacterium animalis on human IBS
[Guyonnet D., 2007]. – Probiotics mixtures, including Lactobacillus acidophilus, L. plantarum,
Lactobacillus rhamnosus, Bifidobacterium breve, Bifidobacterium lactis, Bifidobacterium longum, and Streptococcus thermophilus were used. (Cha 2013) RCT
•
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Effect on probiotics on IBS still remains controversial. Enteric nerve cells
Act on stabilization and immunomodulatory effect on the intestinal microbiota and mucosa
Decrease irritability via enteric nerve cells in the lumina properia. (Groeger D., 2013].
Helicobacter Pylori Infection
• The presence of clarithromycin-resistant H. pylori, eradication is significantly attenuated. (Ushiyama et al.2003) Lactobacillus gasseri inhibited both the in vitro growth of
clarithromycin-resistant H. pylori and the release of interleukin-8 from epithelial cells, H. pylori colonization was significantly decreased by L. gasseri.[Ushiyama et al.2003 ]
Induce inhibition of H. pylori growth and adhesion to epithelial cells and an effect on the host immune system.
Modify eradication rates and antibiotic-associated
gastrointestinal side effects.[Hamilton-Mille2003]
Probiotic-
Probiotics have been suggested to increase efficacy of eradication therapy by: preventing antibiotic-associated side effects and thus
increasing compliance. significantly lower incidence of antibiotic-associated
diarrhea and taste disturbance (Bacillus Clausii ). [Cremonini F 2002] (Loris et al 2016 Expert Rivew G&H )
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Probiotics useful in Celiac Disease
Probiotics :Lactobacillus and Bifidobacterium(Desousa 2014 Clin Microbiol Rev).
• Alter intestinal microbiota composition and fermentation derived metabolite by : regulating epithelial cell barrier function modulating immune response (Licciardi PV et al 2002 , Gut Pathol.2-24 )
• Dietary changes help alleviate the severity of celiac disease for some patient, ameliorate inflammation to a varying degrees ,(Collado et al2008)
Synbiotics :manipulate the intestinal microbiota and could improve the quality of life for celiac patients ,especially on associated disease such type 1 diabetes and other autoimmune disorders (eczema herpitiforme )
(RossiMet al 2010 journal of Leukocyte Biology 87:749-751)
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Probiotics & Pancreatitis
• The safe use of probiotics are raised by the outcomes of several clinical trials.( Ridwan 2008 )
– A mixture of six probiotic bacteria (L. acidophilus, L. casei, L. salivarius, L. lactis, B. bifidum, and B. infantis) used to treat patients with severe acute pancreatitis ,
Increased their risk of mortality ,!!!!!!– although this bacterial mixture inhibited the growth of most
pathogens that caused pancreatitis complications in the preclinical animal studies. (Snydman 2008 Clin Infect Dis)
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Lactose intolerance• Application of pre- and probiotics to improve the clinical symptoms of
lactose intolerance
Lactobacillus delbrüeckii in a milk product can deliver β-galactosidase activity.
Lactobacillus bulgaricus and Streptococcus thermophiles alleviate the lactose intolerance through their enzyme lactase when the product reaches the intestinal tract.
• lactose intolerance can be reduced by β-galactosidase enzyme of the lactic acid bacteria which present in them. ( Masood et al. 2006)
(Roel J. Vonk 2012) Meta-analysis show inconsistent results (Levri et al. J Fam Pract 2005)
Benefit remains unproven.
Probiotics have an effect by two levels:1.The Hydrolysis of lactose in the milk product 2.The hydrolytic capacity of probiotic to reduce the actual amount of lactose
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Probiotics and Hepatic Encephalopathy
Probiotics (VSL#3 or lactobacillus species.)are more effective than placebo in;– Reducing hospitalizations among cirrhotic patients,– Improving MHE, (minimal hepatic encephalopath)– Preventing progression of MHE to OHE. (overt HE)
• Probiotics appear to have similar effectiveness to lactulose in regard to these outcomes.
• The potential role of probiotics in the treatment of minimal hepatic encephalopathy in patients with cirrhosis.”still in research.
S Saab et al2016
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Other GI Disorders
Collagenous Colitis: Possible benefit of E.coli Nissle 1917 (Tromm et al. Z Gastroenterol 2004)
Placebo-controlled trial: Combination of Lactobacillus acidophilus and Bifidobacterium animalis caused improvement in symptoms but had no significant effect on primary endpoints (Wildt et al.Inflamm Bowel Dis 2006)
.
Diverticular Colitis: Combination of VSL#3 and an oral beclomethasone Mezalamine ,was beneficial in a case serie .(Tursi et al. 2008,floch etal2013)
Meta- analysis Cochrane Database Syst Rev. 2008 : No evidence for the effectiveness probiotics!!!!!!!!!!!Alone …..
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Summary • Probiotics are a therapeutic class being increasingly used for a variety of GI disorders.
• Probiotics appear to alter intestinal microflora and may exert their effect's) by a variety of
mechanisms.
• Many species of probiotics exist and it is generally accepted that all probiotics are not created
equal.
• Efficacy may be due to a single strain or multiple strains or a combination of different
probiotics.
• Probiotics do not provide additional benefit compared with standard therapy alone.
.
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CONCLUSION
Are PROBIOTICS
THE SAVORS
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• Dr Amal Nous MD--Makassed University General Hospital Clinical lecturer Beirut Arab University Beirut, Lebanon
• Dr Dania Tabash – MGH chief resident ,Pediatric Department
• Miss Lubna Sino – Secretary research Department
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THE ANNUAL MEETING Pan Arab Societies Pediatric Gastroenterology ,Hepatology & Nutrition
PASPGHAN- 2017Beirut -Lebanon
General secretary of PASPGHAN Prof. Nezha Mouane (Morocco ) President of the congress Asc.Prof Aziz Koleiat( Lebanon )
SEPTEMBER 2017
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Dr Aziz Koleilat Associate professor Beirut Arab University
Makassed University General HospitalPediatric gastroenterology and Nutrition& AsthmaIBR member
GINA Meditrenian group , lebanon representative
Vice general secretary PASPGHAN Pan Arab Society,Pediatric Gastro Enterology Hebatology & Nutrition . [email protected] (Skyp. Whatsup)
MUGH
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Criteria for use a probiotic• It must be safe for consumption:
– Not pathogenic or carrying antibiotic resistance genes– Not degrading to intestinal mucosa or conjugating for bile
acids• It must survival intestinal transit: Acid and bile tolerant• It must adhere to mucosal surface and colonize the intestine
(at least briefly,)• Produce antimicrobial substances and antagonize pathogenic
bacteria• At least one phase 2 study documenting benefit.• It must be stable during processing and storage……. (Borchers et al. 2009)
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Misconception with probiotics• All probiotic supplements are basically the same.• Could have different effects on health.• Can replace medications.• Food and supplement labels provide accurate microbe counts.• Yogurts are generally a good source of probiotics.• The More Strains The merrier and better .• The Higher the Number of Billions, the Better.• The Best Probiotics are Kept in the Fridge. • lyophilisation ensure that the probiotics remain viability at room
temperature.• Probiotics may not be used while taking antibiotics Course.
www.livescience.chelp probiotics-myths.html 2014
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COLONIZATION• A common misconception is that probiotics must always colonize the
intestinal tract to exert their effects.
• Some probiotics (e.g., Bifidobacterium longum and Bacteroides thetaiotamicron) become part of the human intestinal microflora, whereas others (e.g., Lactobacillus casei and B. animalis) may not .
• Non colonizing probiotics indirectly exert their effects either in a transient manner as they pass through or, more likely, by remodeling or influencing the existing microbial community .
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Infection: • Infective endocarditis or bacteremia (Extremely rare-) represent 0.05% -
0.4%
• liver abscess caused by lactobacillus rhamnosus (500 ml/d). Recovered with surgical drainage and antibiotics.
.
Safety of using probiotics
Review of 200 cases of lactobacillus infection 1950-2003;
114 cases of bacteremia*Mortality rate 32%All patients had significant morbidity including
malignancy62 cases of endocardidtis with 22.9% mortality rate. (Cannon et al. Eur J Clin Microbiol Infect Dis 2005.)
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Safety PROBIOTICS
disadvantages Kelli Cooper 2013
• Metabolic and enzymatic effect :theoretically may have some effect on metabolism of bile salts and mucous. (not reported yet )
• Immunological effects : when we have immunodeficient patient and ingest large amount of certain probiotics cause relapse of autoimmune reactions.
• Gene transfer: if genetically modified probiotics used may harbor antibiotic resistant genes.
Risk is transferring of antibiotic resistance genes to the host, as L. reuteri and L. plantarum have been found to carry such genes. (Egervarn MJ
Appl Microbiol. 2009)
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The use of probiotics during pregnancy, in neonates, and in children has not been associated with any adverse immunologic effects,(SrinivasanJ Pediatr Gastroenterol Nutr 2006)
Safety PROBIOTICS disadvantages Kelli Cooper 2013
Infection : when probiotics, given to persons with severe underlying disease, may cause systematic infection.
Bacteremia and fungemia , occurrence in ill patients and immuno deficient individuals has also been reported . (Roy M Robins 2006)
Bacteremia reported in premature babies with short-gut syndrome (Hala fatima 2010)
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Dosage Recommended Dosage for Probiotics
• Different brands of probiotics can contain anywhere from one to 10 billion colony-forming units or CFUs.
• To maintain a healthy digestive tract, a probiotic with one to two billion CFUs is recommended.
• However, if you are taking antibiotics, or if you have symptoms of a bacterial imbalance such as diarrhea, you can take a probiotic with up to 10 billion CFUs until the problem clears up.
• To maintain microorganism balance, take a probiotic of one to two billion CFUs daily or every other day.
• To correct a problem, probiotics containing 10 billion CFUs can be taken daily for up to two weeks. -
Updated: Apr 21, 2015 | By Beverly Bird
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Dose of probiotics for neonates• The probiotic supplementation in infants should be done carefully,
especially those who are preterm because preterm of impaired immune system, poor nutrition, and frequent exposure to harmful microorganisms.
• Recommended - Neonates (less than 32 weeks age of gestation): 3 x 109 cfu/day- Extremely low birth weight infants: 1.5 x 109 cfu/day until they reach
enteral feeds of 50-60 ml/kg/day
- The probiotic dose should be diluted in 1.0 to 1.5 mL of breastmilk or water.
Health and medicine dr Rega 2013
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Facts about Probiotics• Not all Probiotics have same action and functions • Probiotics are specific strains • Probiotics are not absolute treatment , mainly adjuvant , ameliorate
inflammation• There are side effects for probiotics , fungioma , carditis• Probiotics absolutely not effective in pancreatitis • Probiotics are not a treatment for asthma
2015
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Interestingly, reduced microbial diversity was associated with diseases such as Crohn’s disease [Manichanh et al. 2006] and eczema in early life. [Forno et al. 2008]
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As with diseases• Most probiotics tested to date are more effective than placebo in
inducing or maintaining IBD remission
• There is good evidence to support the efficacy of S. boulardii and LABs
and the combination of the two for AAD, VSL#3 for pouchitis, and B.
infantis 35624 for IBS.
• Probiotics decrease the duration of symptoms in acute infectious
diarrhea.
• Probiotics, including E. coli Nissle 1917, LGG, and VSL#3 are as effective
as standard therapy (mesalamine) in inducing or maintaining remission
in UC or CD. When added to standard therapy,
Summary
. Need to be evaluated
AAD-Antibiotic associated diahrea
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As with safety• Probiotics have been shown to be safe in immunocompetent hosts in an outpatient
setting.
• Administration of probiotics to immunocompromised, chronically ill, hospitalized
patients with GI disorders, and indwelling catheters may predispose to probiotic
sepsis, probiotics may increase translocation of bacteria into the bloodstream.
Summary
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What MUST be finally resolved
• Optimal doses,
• Duration of treatment,
• Comparison of different strains and different probiotics,
• Single versus combination probiotics,
• Combination of probiotics with prebiotics,
• Efficacy of various probiotics in different disease states,
• Safety of probiotics in debilitated patients
• Safety in patients with compromised gut epithelial integrity
EPI LONDON 2016
Where PROBIOTICS will lead us???
Thank you AGAIN