1. ROLE OF PROBIOTICS IN ADULT
GASTROENTEROLOGY
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 PROBIOTICS
Elie Metchnikof (1845-1916)
Lactic acid bacteria can render a great
service in the fight against intestinal
putrefaction‟
„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 ITS
INFLUENCE ON HEALTH
O’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 human
disease: Infections, Obesity, Diabetes, NEC, IBS, IBD
PNAS March 15, 2011 Suppl.

9. PROBIOTICS
 Lactobacillus sp.
 reuteri
 casei
 ramnosus
 acidophilus
 Streptococcus sp.
 Bifidobacterium sp.
 infantis
 lactis
 longum
 breve
 bifidum
 Sacharomyces boulardii
(non-human)
 VSL no.3

10. DESIRABLE CHARACTERISTICS OF A
PROBIOTIC 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 a
treatment?
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 GG
Results
 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 Constipation
Rationale
 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 help
lower gut pH and stimulate motility
- Some metabolic products act as neurotransmitters
which affects motility.
•Research
•Endpoints: symptom questionnaires-pain,
bloating, completeness of evacuation, stool
consistency defecation frequency, transit time
measurements
•Hoveyda & Whorwell et al-improvement in 3D
with Bifidobacterium infantis 35624(BMC
Gastrointestinal-2009)
•Evidence is accumulating for some other
strains also

17. CONSTIPATION
Krammer 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 results
Conclusion?: more high quality data (RCT‟s) are required!
Eamonn et al Nutr clin Pract 2012

19. INFLAMMATORY BOWEL DISEASE
Mitsuyama 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 in
Infective & antibiotic ass. diarrhoea.
•+ve Role of Probiotics in Pouchitis & UC but
in Crohn‟s??
•MicrObesity- a new concept about microbial
community participating in development of
fat deposition,insulin resisitence & NAFLD
•Pre/pro/symbiotics improve MHE
significantly(almost as good as lactulose)
•Biologic effects of probiotics are likely to be
strain specific.

24. Thank You