1. GUT Microbiota in health and disease
Moderator – Dr Sunil K Mathai
Panelists –
Dr Benoy Sebastian, Dr Geetha M,
Dr Antony Chettupuzha, Dr Joseph John

2. GUT : How sterile is it? – AC

4. Sterile at birth…

5. 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

7. Infant feeding: Role in development of GUT microbiota - GM

8. 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

9. GUT Microbiota a Vital organ – BS

10. 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

11. Hidden Metabolic Organ

12. Protective Function Pathogen Displacement Antimicrobial factors
Immune system development
Promotes anti inflammatory cytokines and down regulates pro inflammatory cytokines
Induces regulatory T cells

13. Structural Functions Barrier Fortification Induction of IgA
Apical tightening of tight junction
Enhanced mucin prodution

14. Metabolic Functions Short chain fatty acids
Metabolizes dietary carcinogens
Synthesis of vitamins
Ion absorption

15. GUT Microbiota in Growth and Development – GM

16. GUT microbiota in growth and development
Gut and microbiotia – symbiotic relationship
Modulates gut immune system via “ cross-talk”

18. In the newborn period commensal bacteria provide the immune system with stimuli which causes maturation
If you get the right bacteria – prevents a number of AI conditions, atopy, allergy etc

19. GUT dysbiosys – Good, Bad and Ugly – JJ

20. Good

21. 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

22. Bad

23. Ugly

24. Probiotic, Prebiotic and Synbiotic – The concept – AC

25. Probiotic 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 1907
Parker, R. B Probiotics, the other half of the antibiotic story. Anim. Nutr. Health. 29:4-8
Fuller, R Probiotics in man and animals. J. Appl. Bacteriol. 66:
Ilya Ilyich Mechnikov

26. Non-digestible Oligosaccharides
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.”
They are dietary fibers with a well-established positive impact on the intestinal microflora
Non-digestible Oligosaccharides
Inulin
Oligofructose
(trans)galactooligosaccharides
Term coined by Glen Gibson 1995

27. Synbiotics

28. Selection of a Probiotic candidate – Which organism and why – BS

29. A probiotic strain is identified by the genus, species, and an alphanumeric designation

30. 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

31. Clinically Useful strains
Lactobacillus sp.
reuteri
casei
ramnosus
Acidophilus
Streptococcus sp.
Bifidobacterium sp.
Infantis (breastmilk)
lactis
longum
breve
bifidum
Sacharomyces boulardii
Enterococcus sp
Mixtures

32. Before marketing Purified strain of microbe
In vivo safety and efficacy studies in animals
In vivo safety,efficacy and effectiveness studies in human beings

33. Labeling Requirements
Genus,species and strains
Minimum valuable number of each probiotic strain at which efficacy is claimed
Shelf life
Evidence based health claims
Serving size
Storage conditions

35. Mechanism of action of Probiotics JJ

36. 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

37. 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

40. Daily Kerala diet; Is it probiotic rich? GM

41. Daily Kerala Diet – is it probiotic rich?
Traditional fare –
Fermented rice
Healthy and “prebiotic rich”
Newer diets
Neither healthy nor probiotic rich
Added probiotics may benefit

42. Available probiotic preparations; are all the same? AC

43. Probiotic Platter VSL#3 ECONORM BECELAC-PB DAROLAC BIFILAC
ENTEROGERMINA bacillus clausii
VSL#3
 Streptococcus thermophilus , bifidobacterium breve , bifidobacterium longum , bifidobacterium infantis , lactobacillus acidophilus , lactobacillus plantarum , lactobacillus paracasei , lactobacillus delbrueckii spp bulgaricus.
DAROLAC
 lactobacillus acidophilus lactobacillus rhamnosus bifidobacterium longum Saccharomyces boulardii.
BIFILAC
 Streptococcus lactobacillus
clostridium butyricum bacillus mesentericus
VELGUT
 lactobacillus acidophilus , lactobacillus plantarum , lactobacillus casei , lactobacillus rhamnosus , bifidobacterium breve , bifidobacterium longum , bifidobacterium infantis , Streptococcus thermophilus , Saccharomyces boulardii fructooligosaccharides
YOGUT
oligofructose ,
lactobacillus acidophilus ,
lactobacillus rhamnosus , bifidobacterium bifidum , bifidobacterium infantis , bifidobacterium longum.
ECONORM
Saccharomyces boulardii
BECELAC-PB
Streptococcus faecalis clostridium butyricum bacillus mesentericus lactobacillus sporogenes
PREPRO
Streptococcus faecalis clostridium butyricum bacillus mesentericus lactobacillus acidophilus
PRO-GURT
: , fructo oligosaccharide 100 mg, lactobacillus acidophilus 700 million cells, lactobacillus rhamnosus 400 million cells, lactobacillus paracasei 300 million cells, lactobacillus plantarum 300 million cells, lactobacillus bulgaricus 300 million cells, bifidobacterium longum 300 million cells, bifidobacterium infantis 300 million cells, bifidobacterium breve 300 million cells, Streptococcus thermophilus 400 million cells, Saccharomyces boulardi

44. Are all the same?

45. Indications of Probiotics in Adults BS

46. 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 – superior

47. Diarrhoea Clinical condition Effectiveness Organisms
Infectious Diarrhoea A
S.boulardii,LGG
Prevention of Antibiotic associated diarrhoea
S.boulardii,LGG,L.casei,S.thermophilus
Prevention of PMC B
LGG,S.boulardii
Treatment of PMC
Prophylaxis of Travellers Dirrhoea

48. 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

49. 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

50. Other GI Diseases Disease Comments H.Pylori
Significant reduction in AAD.No difference in eradication rates
Lactose Intolerance
Significant benefit
Hepatic Encephalopathy
Role in MHE.Lactulose – a prebiotic
No proven in overt HE
NASH
Emerging data
Radiation Enteritis
Effect is only minimal

51. Indications of Probiotics in infants and Children GM

52. 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)

53. Other indications ( Value not proven)
IBD
IBS
H Pylori

54. Dosage and Administration of Probiotics; Issues to consider JJ

55. 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 × 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.

56. 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.

57. Disorder, action
Probiotic strain / prebiotic
Recommended dose
Maintenance of remission in ulcerative colitis
Escherichia coli Nissle 1917
5 × 1010 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 × 1011
cfu, twice daily
Prevention and maintenance of remission in pouchitis
2 × 4.5 ×1011
Alleviates some symptoms of irritable bowel syndrome
Bifidobacterium
infantis 35624
108 cfu, once daily
B. longum 101 (29%), L. acidophilus 102 (29%), Lactococcus lactis 103 (29%), and S. thermophilus 104(13%)
1010 cfu, once daily
Treatment of acute diarrhea in adults
Enterococcus faecium LAB SF68
108 cfu, three
times daily
Saccharomyces. boulardii, strain of S. cerevisiae
109 cfu per capsule of 250mg, 2–6
capsules per day

58. Disorder, action
Probiotic strain / prebiotic
Recommended dose
Prevention of antibiotic associated diarrhea in adults
E. faecium LAB SF68
108 cfu, twice daily
S. boulardii, strain
of S. cerevisiae
1 g or 4 × 109 cfu per day
L. rhamnosus GG
cfu, twice daily
Prevention of C. difficile diarrhea
in adults
2–3 × 109 cfu for
28 days, followed for
another 4 weeks
L. rhamnosus
HN001 + L. acidophilus
NCFM
109 cfu each, once daily
L. acidophilus + B. bifidum (Cultech strains)
2 × 1010 cfu each strain, once daily

59. Safety of Probiotics. Are they safe in CLD, CKD, Immunosuppressed AC

61. No notable adverse effects
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

62. Lumia, Clin Gastroenterol Hepatol. 2014
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

63. 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

64. Extra GI uses of probiotics BS

65. 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

66. Fecal Transplantation JJ

67. 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. 

68. 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.

69. 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.

70. Concluding remarks

71. Thank you