5Gut MicrobiotaNumber of intestinal microbial cells is 10 times greater than the number of human body cellsApproximately 150 times larger than the human gene complement, with an estimated set of 3.3 million microbial geneFirmicutesBacteroidesProteobacteriaCyanobacteriaFusobacteriaVerrucomicrobiaActinobacteria
7Infant feeding: Role in development of GUT microbiota - GM
8Infant feeding – Role in devpt of microbiota Best microbiota in babies born by vaginal delivery , roomed-in with mother & breast-fedWorst in ceasarian delivery, admitted in ICU, formula-fed and administered IV antibiotics
10Microbial ecosystem Upto 100 trillion bacteria - 500 different species Outnumber human somatic and germ cells by 10 foldMarked microbial diversity among different individualsEach person has his own distinctive pattern of microbial compositionDetermined by genetic and environmental factors
21Dysbiosis is a state in which the microbiota becomes altered due to an alteration in the composition of the microbiota, a change in bacterial metabolic activity and/or a shift in local distribution of communities.Role in several diseases.Factors altering the gastrointestinal ecosystem includeantibiotics,psychological and physical stresses,radiation,altered peristalsis anddietary changes
24Probiotic, Prebiotic and Synbiotic – The concept – AC
25Probiotic means for life… WHO definition(2001): “Live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host”Lilly, D. M. and R. H. Stillwell Probiotics: growth promoting factors produced by microorganisms. Science 147:Sour milk with lactobacilli prolongs life 1907Parker, R. B Probiotics, the other half of the antibiotic story. Anim. Nutr. Health. 29:4-8Fuller, R Probiotics in man and animals. J. Appl. Bacteriol. 66:Ilya Ilyich Mechnikov
26Non-digestible Oligosaccharides PrebioticDefinition: “A dietary prebiotic is a selectively fermented ingredient that results in specific changes, in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health.”They are dietary fibers with a well-established positive impact on the intestinal microfloraNon-digestible OligosaccharidesInulinOligofructose(trans)galactooligosaccharidesTerm coined by Glen Gibson 1995
28Selection of a Probiotic candidate – Which organism and why – BS
29A probiotic strain is identified by the genus, species, and an alphanumeric designation
30An ideal probioticAble to survive the passage through the digestive systemAble to attach to the intestinal epithelia and colonise.Able to maintain good viabilityAble to utilise the nutrients and substrates in a normal dietNon pathogenic and non toxicCapable of exerting a benificial effect on the hostStability of desired characteristics during processing, storage and transportation
36Antimicrobial actions: Inhibit growth of pathogenic enteric bacteria by:Decreasing luminal pHSecreting bactericidal proteinsResisting colonisationCompeting for nutrients with pathogensModifying pathogen-derived toxinsStimulating defensin productionBlocking epithelial bindingStimulating mucus production
37Barrier function:Improve epithelial and mucosal barrier function by:Producing SCFAsIncrease barrier integrityEnhance mucus productionImmune function:Alter host immune response by:Modulating cytokine profiles - induce IL-10 and TGF- secretion and decrease TNF and IFN- expressionActivating local macrophages and increase secretory IgA production both locally and systemicallyActivating Treg cellsInducing hyporesponsiveness to food antigensDampening inflammatory responses
46Irritable Bowel syndrome Metaanalysis - Moyyedi et al Gut 201019 RCTs – 1650 patientsSignificant reduction in symptoms with an NNT of 4Trend towards improving pain and bloatingNo effect on constipationBifidobacterium infantis – superior
47Diarrhoea Clinical condition Effectiveness Organisms Infectious DiarrhoeaAS.boulardii,LGGPrevention of Antibiotic associated diarrhoeaS.boulardii,LGG,L.casei,S.thermophilusPrevention of PMCBLGG,S.boulardiiTreatment of PMCProphylaxis of Travellers Dirrhoea
48Inflammatory Bowel Disease Yet to meet the high expectations predicted by the theoretical dataNo significant or consistent benefit in Crohn’s diseaseIn UC a modest effect in inducing and maintaining remession in mild to moderate UCEscherichia coli Nissle and VSL # 3
49Pouchitis Significant reduction first episode of pouchitis Maintenance of remission of recurrent or refractory pouchitisUsed VSL # 3Gosselink etal Dis Colon Rectum 2004Mimura et al Gut 2004
50Other GI Diseases Disease Comments H.Pylori Significant reduction in AAD.No difference in eradication ratesLactose IntoleranceSignificant benefitHepatic EncephalopathyRole in MHE.Lactulose – a prebioticNo proven in overt HENASHEmerging dataRadiation EnteritisEffect is only minimal
51Indications of Probiotics in infants and Children GM
52Indications of probiotics in Infants an children Definite indicationsAntibiotic induced diarrhoea(Probiotics for the Prevention and Treatment of Antibiotic-Associated Diarrhea - A Systematic Review and Meta-analysis. JAMA. 2012)Traveller’s diarrhoeaRotaviral DiarrhoeaNecrotizing Enterocolitis(Probiotics Reduce All-Cause Mortality and Necrotizing Enterocolitis. Pediatrics 2010)
53Other indications ( Value not proven) IBDIBSH Pylori
54Dosage and Administration of Probiotics; Issues to consider JJ
55Pay close attention to the strain (not just the genus and species). Different probiotic strains exert their beneficial effects via different mechanisms and may be synergistic with other microbiota.Studies have used doses ranging from 2 × 107 colony-forming units (CFU) per day to 3.2 × 1012 CFU per day.No uniform dosing recommendations.Frequency can range from twice daily to intermittent weekly.
56Probiotic strains are generally safe. Lactobacilli and bifidobacteria are normal commensals of the GI tract.Because probiotics are viable microorganisms, they have the potential to cause invasive infections in hosts with compromised mucosal epithelia.Should be used with caution in children, elderly persons and individuals with major risk factors.
57Disorder, actionProbiotic strain / prebioticRecommended doseMaintenance of remission in ulcerative colitisEscherichia coli Nissle 19175 × 1010 viablebac, twice dailyTreatment of mildly activeulcerative colitis or pouchitisVSL# 3 mixture of eight strains (one S. thermophilus, four Lactobacillus,three Bifidobacterium)2 × 9 × 1011cfu, twice dailyPrevention and maintenance of remission in pouchitis2 × 4.5 ×1011Alleviates some symptoms of irritable bowel syndromeBifidobacteriuminfantis 35624108 cfu, once dailyB. longum 101 (29%), L. acidophilus 102 (29%), Lactococcus lactis 103 (29%), and S. thermophilus 104(13%)1010 cfu, once dailyTreatment of acute diarrhea in adultsEnterococcus faecium LAB SF68108 cfu, threetimes dailySaccharomyces. boulardii, strain of S. cerevisiae109 cfu per capsule of 250mg, 2–6capsules per day
58Disorder, actionProbiotic strain / prebioticRecommended dosePrevention of antibiotic associated diarrhea in adultsE. faecium LAB SF68108 cfu, twice dailyS. boulardii, strainof S. cerevisiae1 g or 4 × 109 cfu per dayL. rhamnosus GGcfu, twice dailyPrevention of C. difficile diarrheain adults2–3 × 109 cfu for28 days, followed foranother 4 weeksL. rhamnosusHN001 + L. acidophilusNCFM109 cfu each, once dailyL. acidophilus + B. bifidum (Cultech strains)2 × 1010 cfu each strain, once daily
59Safety of Probiotics. Are they safe in CLD, CKD, Immunosuppressed AC
61No notable adverse effects Pre-, Pro-, and Synbiotics: Do They Have a Role in Reducing Uremic Toxins? A Systematic Review and Meta-AnalysisRossi, Int J Nephrol. 201219 studies analysedSupportive evidence for the effectiveness of pre- and probiotics on reducing toxinsNo notable adverse effects
62Lumia, Clin Gastroenterol Hepatol. 2014 Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trialLumia, Clin Gastroenterol Hepatol. 2014160 subjectsNew DelhiFound to be effective in preventing HE in patients with cirrhosisNo adverse effects noted
63The efficacy and safety of probiotics in people with cancer: a systematic review Redman, Ann Oncol 201417 studies analyzed1530 patients5 case reports showed probiotic-related bacteraemia/fungaemia/positive blood cultures
67Fecal microbiota transplantation (FMT) is the process of transplantation of fecal bacteria from a healthy individual into a recipient.Involves restoration of colonic flora by introducing healthy bacterial flora through infusion of stool from a healthy human donor. First description of FMT published in 1958 by Eiseman and colleagues, surgeons from Colorado, who treated four critically ill patients with fulminant pseudomembranous colitis.
68Hypothesis behind FMT rests on concept of bacterial interference. Production of antimicrobial agents (Bacteriocins) by the introduced colonic flora.Highly effective in treating recurrent C. difficile, and more effective than vancomycin alone.Also used to treat other conditions including ulcerative colitis, constipation, irritable bowel syndrome and neurological conditions like multiple sclerosis and Parkinson’s disease.
69Single to multiple infusions. Donors tested for a wide array of bacterial and parasitic infections.Infusions administered via various routes depending on suitability and ease - enema, colonoscope.Modified form of fecal bacteriotherapy (Autologous Restoration of Gastrointestinal Flora - ARGF) Autologous fecal sample provided by the patient before medical treatment is stored. Should the patient develop C. difficile, the sample is extracted with saline and filtered. The filtrate is freeze dried and enclosed in enteric coated capsules.