1. ROLE OF PROBIOTICS IN ADULTGASTROENTEROLOGY Dr Ajay Bhalla Principal Consultant & HOD Gastroenterology Fortis Hospital Noida
2. PROBIOTICS For life “You’ve been fooling around with alternative medicine, haven’t you?”
3. HISTORY OF PROBIOTICSElie Metchnikof (1845-1916)Lactic acid bacteria can render a greatservice in the fight against intestinalputrefaction‟„Postpone and ameliorate old age‟The Prolongation of Life (1908)
4. PROBIOTICS: DEFINITIONS World Health Organization: “live microorganisms which when administered in adequate amounts confer a health benefit on the host” A bacterial strain that: Survives the stomach acid and bile Adheres to intestinal lining Grows and establishes temporary residence in the intestines Imparts health benefits R Fuller. Probiotics: The Scientific Basis. London: Chapman and Halls. 1992
5. PROBIOTICS Colonization at birth Similar to maternal species Specific organisms vary by age in first year but become established by 1 year No. of bacteria in gut 10 times the total no. of body cells. Composition of each individuals microbiota is so distinctive…..it could be used as an alternative to fingerprints..! Composition also influenced by age,socio- economic srroundings & use of antibiotics
6. THE GUT MICRO BIOTA AND ITSINFLUENCE ON HEALTHO’Hara A.M. et al. EMBO reports 2006; 7: 688-693.
7. DISTRIBUTION OF MICROBES IN THE GUT Present in all parts of the intestinal tract Increase from esophagus to colon acid production bile motility ileocecal valve Surface-lumen axis: more anaerobes in the outer mucus Bacteria are not in direct contact with the mucosa – at least, in healthy subjects Microbes in Intestinal Health and Disease; A.S. Neish Gastroenterology 2009;136:65-80
8. Dysbiosis in the Gut Disturbance of the balance of the intestinal microbiota Stress Diet Ageing Infection Medication (Antibiotics)Increasingly recognized as a risk factor for humandisease: Infections, Obesity, Diabetes, NEC, IBS, IBDPNAS March 15, 2011 Suppl.
10. DESIRABLE CHARACTERISTICS OF APROBIOTIC STRAIN Stable and well-described microbe Non-toxic, non-pathogenic Able to survive and multiply in desired location Able to combat pathogens Efficacious in promoting specific health claim Scalable production Easy to distribute
11. Mechanism of Action
12. Scientific Evidence for Probiotics In vitro studies, In vivo animal studies, Human observational/epidemiology studies ,Human experimental studies, Randomized Double Blind Placebo Controlled studies with validated biomarkers In 2010, there were 1158 articles: in high ranking peer-reviewed journals; increasing DBPCRTs …. Meta-analyses are usually based on a generic probiotic benefit Reviews and meta-analyses will include relevant trials with different strains but generic conclusions may not be true for individual strains Each Probiotic strain to be supported by its own dossier of scientific evidence…
13. Benefits and Application Preventive and therapeutic modality for gastrointestinal disorders such as Antibiotic associated & infectious diarrhoea, IBS, IBD, Management of NAFLD,MHE & Hepatitis Immune stimulation Prevention of allergic disorders Prevention of chronic inflammatory diseases Prevention of cancers Reduction of respiratory diseases
14. INFECTIOUS DIARRHOEA – PROBIOTICS AS A TREATMENT ? Allen et al (2010) Cochrane Systematic Review Used alongside rehydration therapy, probiotics appear to be safe and have clear beneficial effects in shortening the duration and reducing stool frequency in acute infectious diarrhoea. Wolvers et al (2010) Review Moderate to significant benefit of many probiotic strains in management of acute watery diarrhoea (RV infections) in children. • Moderate improvements in acute infections (~1 day ↓ duration diarrhoea) • Significant improvements in watery diarrhoea and viral gastroenteritis • More evident when intervention started early in course of infection The use of probiotics for acute infectious diarrhoea in children is an accepted therapy in Europe Recommended by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition & European Society of Paediatric Infectious Diseases Expert Working Group
15. Functional Constipation(IBS) – probiotics as atreatment?Chimielewska et al (2010) Systematic Review 5 RCT‟s , N= 377 ( 266 adults , 3 RCT‟s and 111 children, 2 RCT‟s) Bifidobacterium lactis DN-173 010, Lactobacillus casei Shirota,Escherichia coli Nissle 1917, Lactobacillus casei rhamnosus Lcr 35,Lactobacillus rhamnosus GGResults Bifidobacterium lactis DN-173 010, Lactobacillus casei Shirota and Escherichia coli Nissle 1917 are effective in improving defecation frequency and stool consistency in adults. In children, Lactobacillus casei rhamnosus Lcr 35 shows a beneficial effect. Lactobacillus rhamnosus GG did not demonstrate any benefit
16. Probiotics and ConstipationRationale Some evidence of - Aberrant microbiota - Antibiotic benefit - Link with methane oxidation Up to 66% of the dry weight of stool is bacteria Microbial production of SCFA and metabolism of bile acids helplower gut pH and stimulate motility - Some metabolic products act as neurotransmitters which affects motility.•Research•Endpoints: symptom questionnaires-pain,bloating, completeness of evacuation, stoolconsistency defecation frequency, transit timemeasurements•Hoveyda & Whorwell et al-improvement in 3Dwith Bifidobacterium infantis 35624(BMCGastrointestinal-2009)•Evidence is accumulating for some otherstrains also
17. CONSTIPATIONKrammer HJ Coloproctology 2011, 33: 109-113 Double blind Randomized Placebo Controlled trial (n=24) Yakult or placebo daily for period of 4 weeks Significant acceleration of the total colonic transit time from 95.6 h to 76.5 h (p=0.05) in probiotic group; No statistically significant change in the total colonic transit time (before: 95.8 h, after: 87.1 h, p=0.282) in the placebo group
18. Probiotics in IBD Still evolving and contentious..microbiota as cause?? Pouchitis: positive reports (in adults), with a mixture of bacterial strains(VSL3)-85% remission vs 6%(Mimura et al 2004 GUT) Ulcerative Colitis: some positive effects - maintenance of remission - induction of remission in mild-mod flare ups Crohn disease:minimal- no benefit Choice of strain, dosing, and disease activity severity might well account for variable resultsConclusion?: more high quality data (RCT‟s) are required! Eamonn et al Nutr clin Pract 2012
19. INFLAMMATORY BOWEL DISEASEMitsuyama K et al J Clin Biochem Nutr 2008, 43 (Suppl.1):78-81 An open label preliminary trial conducted on 10 patients with mildly to moderately active Ulcerative Colitis (UC) Intervention: LcS (8x1010 CFU/day) in addition to conventional therapy daily for 8 weeks Significantly better clinical activity index score seen after LcS treatment as compared with pre-treatment and control group LcS effectively treats UC at least in part through the inhibition of interleukin-6 signalling
20. MICROBIOTA & DISEASE Antibiotic associated diarhhoea:Normal microbiota eliminated by antibiotics helps other disease causing bacteria to proliferate(Cl.diff.) Necrotizing Enteroclotitis in premature infants Small Intestinal bacterial overgrowth Bacterial translocation from Gut flora in - Critically ill - Surgery or Trauma - CLD with SBP
21. PROBIOTICS & LIVER DISEASES NAFLD/OBESITY:Qualitative change in Gut microbiota with more avid extractors of absorbale nutrients…hence more Cal. to host(Iacano et al J Nutr Biochem 2010) Hepatic Encephalopathy(MHE):As effective as Lactulose in decreasing Blood Ammonia levels (Changing gut pH by SCFA,decreasing Bacterial urease activity & decreasing intestinal permeability to ammonia)-Shukla et al Aliment Pharmacol Ther 2011. Salmonella induced liver damage prevented by probiotics by decreasing bacterial translocation to liver(Rishi et al FEMS Microbiol Ecol 2009)
22. SAFETY/CAUTION Premature neonates or Immunodef. Infants Short bowel syndrome-Septicemia Severe acute Pancreatitis-Increased Mortality ??? Etiology
23. CONCLUSIONS•Role of Probiotics well established inInfective & antibiotic ass. diarrhoea.•+ve Role of Probiotics in Pouchitis & UC butin Crohn‟s??•MicrObesity- a new concept about microbialcommunity participating in development offat deposition,insulin resisitence & NAFLD•Pre/pro/symbiotics improve MHEsignificantly(almost as good as lactulose)•Biologic effects of probiotics are likely to bestrain specific.