Presentation on theme: "GUT Microbiota in health and disease Moderator – Dr Sunil K Mathai Panelists – Dr Benoy Sebastian, Dr Geetha M, Dr Antony Chettupuzha, Dr Joseph John."— Presentation transcript:
GUT Microbiota in health and disease Moderator – Dr Sunil K Mathai Panelists – Dr Benoy Sebastian, Dr Geetha M, Dr Antony Chettupuzha, Dr Joseph John
Gut Microbiota Number of intestinal microbial cells is 10 times greater than the number of human body cells Approximately 150 times larger than the human gene complement, with an estimated set of 3.3 million microbial gene Firmicutes Bacteroides Proteobacteria Cyanobacteria Fusobacteria Verrucomicrobia Actinobacteria
Infant feeding: Role in development of GUT microbiota - GM
Infant feeding – Role in devpt of microbiota Best microbiota in babies born by vaginal delivery, roomed-in with mother & breast-fed Worst in ceasarian delivery, admitted in ICU, formula-fed and administered IV antibiotics
Microbial ecosystem Upto 100 trillion bacteria - 500 different species Outnumber human somatic and germ cells by 10 fold Marked microbial diversity among different individuals Each person has his own distinctive pattern of microbial composition Determined by genetic and environmental factors
Protective Function Pathogen Displacement Antimicrobial factors Immune system development Promotes anti inflammatory cytokines and down regulates pro inflammatory cytokines Induces regulatory T cells
Structural Functions Barrier Fortification Induction of IgA Apical tightening of tight junction Enhanced mucin prodution
Metabolic Functions Short chain fatty acids Metabolizes dietary carcinogens Synthesis of vitamins Ion absorption
Dysbiosis 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 include antibiotics, psychological and physical stresses, radiation, altered peristalsis and dietary changes
Probiotic, Prebiotic and Synbiotic – The concept – AC
Probiotic means for life… WHO definition(2001): “Live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host” Ilya Ilyich Mechnikov Sour milk with lactobacilli prolongs life 1907 Lilly, D. M. and R. H. Stillwell. 1965. Probiotics: growth promoting factors produced by microorganisms. Science 147:747-748 Parker, R. B. 1974. Probiotics, the other half of the antibiotic story. Anim. Nutr. Health. 29:4-8 Fuller, R. 1989. Probiotics in man and animals. J. Appl. Bacteriol. 66:365-378
Prebiotic Definition: “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.” Term coined by Glen Gibson 1995 They are dietary fibers with a well- established positive impact on the intestinal microflora Non-digestible Oligosaccharides Inulin Oligofructose (trans)galactooligosaccharides
Selection of a Probiotic candidate – Which organism and why – BS
A probiotic strain is identified by the genus, species, and an alphanumeric designation
An ideal probiotic Able to survive the passage through the digestive system Able to attach to the intestinal epithelia and colonise. Able to maintain good viability Able to utilise the nutrients and substrates in a normal diet Non pathogenic and non toxic Capable of exerting a benificial effect on the host Stability of desired characteristics during processing, storage and transportation
Antimicrobial actions: Inhibit growth of pathogenic enteric bacteria by: Decreasing luminal pH Secreting bactericidal proteins Resisting colonisation Competing for nutrients with pathogens Modifying pathogen-derived toxins Stimulating defensin production Blocking epithelial binding Stimulating mucus production
Barrier function: Improve epithelial and mucosal barrier function by: Producing SCFAs Increase barrier integrity Enhance mucus production Immune function: Alter host immune response by: Modulating cytokine profiles - induce IL-10 and TGF- secretion and decrease TNF and IFN- expression Activating local macrophages and increase secretory IgA production both locally and systemically Activating Treg cells Inducing hyporesponsiveness to food antigens Dampening inflammatory responses
Irritable Bowel syndrome Metaanalysis - Moyyedi et al Gut 2010 19 RCTs – 1650 patients Significant reduction in symptoms with an NNT of 4 Trend towards improving pain and bloating No effect on constipation Bifidobacterium infantis 35624 – superior
Diarrhoea Clinical conditionEffectivenessOrganisms Infectious DiarrhoeaAS.boulardii,LGG Prevention of Antibiotic associated diarrhoea AS.boulardii,LGG,L.ca sei,S.thermophilus Prevention of PMCBLGG,S.boulardii Treatment of PMCBLGG,S.boulardii Prophylaxis of Travellers Dirrhoea BLGG,S.boulardii
Inflammatory Bowel Disease Yet to meet the high expectations predicted by the theoretical data No significant or consistent benefit in Crohn’s disease In UC a modest effect in inducing and maintaining remession in mild to moderate UC Escherichia coli Nissle and VSL # 3
Pouchitis Significant reduction first episode of pouchitis Maintenance of remission of recurrent or refractory pouchitis Used VSL # 3 Gosselink etal Dis Colon Rectum 2004 Mimura et al Gut 2004
Other GI Diseases DiseaseComments H.PyloriSignificant reduction in AAD.No difference in eradication rates Lactose IntoleranceSignificant benefit Hepatic EncephalopathyRole in MHE.Lactulose – a prebiotic No proven in overt HE NASHEmerging data Radiation EnteritisEffect is only minimal
Indications of Probiotics in infants and Children GM
Indications of probiotics in Infants an children Definite indications – Antibiotic induced diarrhoea (Probiotics for the Prevention and Treatment of Antibiotic-Associated Diarrhea - A Systematic Review and Meta-analysis. JAMA. 2012) – Traveller’s diarrhoea – Rotaviral Diarrhoea – Necrotizing Enterocolitis (Probiotics Reduce All-Cause Mortality and Necrotizing Enterocolitis. Pediatrics 2010)
Other indications ( Value not proven) – IBD – IBS – H Pylori
Dosage and Administration of Probiotics; Issues to consider JJ
Pay 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 × 10 7 colony- forming units (CFU) per day to 3.2 × 10 12 CFU per day. No uniform dosing recommendations. Frequency can range from twice daily to intermittent weekly.
Probiotic 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.
Disorder, actionProbiotic strain / prebioticRecommended dose Maintenance of remission in ulcerative colitis Escherichia coli Nissle 19175 × 10 10 viable bac, twice daily Treatment of mildly active ulcerative colitis or pouchitis VSL# 3 mixture of eight strains (one S. thermophilus, four Lactobacillus, three Bifidobacterium) 2 × 9 × 10 11 cfu, twice daily Prevention and maintenance of remission in pouchitis VSL# 3 mixture of eight strains (one S. thermophilus, four Lactobacillus, three Bifidobacterium) 2 × 4.5 ×10 11 cfu, twice daily Alleviates some symptoms of irritable bowel syndrome Bifidobacterium infantis 35624 10 8 cfu, once daily B. longum 101 (29%), L. acidophilus 102 (29%), Lactococcus lactis 103 (29%), and S. thermophilus 104(13%) 10 10 cfu, once daily Treatment of acute diarrhea in adults Enterococcus faecium LAB SF6810 8 cfu, three times daily Saccharomyces. boulardii, strain of S. cerevisiae 10 9 cfu per capsule of 250mg, 2–6 capsules per day
Disorder, actionProbiotic strain / prebioticRecommended dose Prevention of antibiotic associated diarrhea in adults E. faecium LAB SF6810 8 cfu, twice daily S. boulardii, strain of S. cerevisiae 1 g or 4 × 10 9 cfu per day L. rhamnosus GG10 10- 10 11 cfu, twice daily Prevention of C. difficile diarrhea in adults S. boulardii, strain of S. cerevisiae 2–3 × 10 9 cfu for 28 days, followed for another 4 weeks L. rhamnosus HN001 + L. acidophilus NCFM 10 9 cfu each, once daily L. acidophilus + B. bifidum (Cultech strains) 2 × 10 10 cfu each strain, once daily
Safety of Probiotics. Are they safe in CLD, CKD, Immunosuppressed AC
Pre-, Pro-, and Synbiotics: Do They Have a Role in Reducing Uremic Toxins? A Systematic Review and Meta-Analysis Rossi, Int J Nephrol. 2012 19 studies analysed Supportive evidence for the effectiveness of pre- and probiotics on reducing toxins No notable adverse effects
Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trial Lumia, Clin Gastroenterol Hepatol. 2014 160 subjects New Delhi Found to be effective in preventing HE in patients with cirrhosis No adverse effects noted
The efficacy and safety of probiotics in people with cancer: a systematic review Redman, Ann Oncol 2014 17 studies analyzed 1530 patients 5 case reports showed probiotic-related bacteraemia/fungaemia/positive blood cultures
And many more……. Recurrent UTI Vaginal infection Atopic diseases Food allergy Recurrent URTI Dental Caries VAP Prevention of cancer Immune Enhancement Cardiovascular Risk Reduction Obesity Type 2 Diabetes mellitus
Fecal 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.
Hypothesis 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.
Single 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.