Prof. Dr. R.V.S.N. Sarma, MD., M.Sc (Canada), RCGP, FCGP, FIMSA, Senior Consultant Physician, Cardio-Metabolic and Chest Specialist Honorary National Professor of Medicine (CGP) visit:

2 Antibotics Probiotics Synbiotics Prebiotics

3 Potential benefits of Lactobacillus~125 yrs ago 1905: Concept of Probiotics

 Starts immediately after birth  Place of birth  Type of Delivery  Feeding: Time, Type  Pre-lacteals vs Exclusive breast feed.  Premature vs. Full term  Sick babies 4

 1 st Year;: > 200 bacterial species  Adult : bacterial species  Elderly: 300 Bact. Species  Chr. Intestinal disorders 5

 For context – Total Cells  Theirs ~ 100,000 billion.  Ours ~ 10,000 billion.

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Friendly bacteria – Probiotics Unfriendly / harmful Bacteria – Pathogens

9 Staph. Aureus, albusNose & skin Mouth, Colon, Vagina Lactobacilus Sp, Bifidobact.. Candida albicansMouth, Colon, Vagina Vagina, Outer urethra E. Coli. Haemophilus Sp. Nasophyrinx & Conjunctiva Pseudomonas aeruginosaColon & skin Facultative AnaerobesStrict anaerobes LACTOBACILLUS: BIFIDOBACTERIA: SACCHAROMYECES:

Probiotics (Friendly Bacteria) Normalise Intestine ImmunomodulationMetabolic effects Suppression of PPMs Intestinal mucosal integrity Regulation of bowel movement IBS Strengthens immunity Alleviate food allergy symptoms Conrol of IBD Production of vitamins; improves digestion Lactose tolerance Lowers cholesterol (Bile acid deconjugation &Secretion)

Inhibit Potentially Pathogenic Microorganisms (PPMs)  Reduction in Intestinal pH ( through production of SCFAs)  Production of bacteriocins  Competitive blocking of adhesion sites  Competition for nutrients

 Most abundant Probiotic in GI  Lactobacillus:  Acidophilus,  Rhamnosus, GG  Plantarum,  Reuteri,  Bulgaricus,  Sporogens  Casei  Action only in Small intestine 14

 Bifidobacteria  32 different species : Longum, Bifidum, infantis etc  Most abundant probiotic next to lactobacilli Sp. in the GIT  Action : Large Intestine 15

 Apart from the general Probiotics effect,  Bifidobacteria helps is Glutamine synthesis  Glutamine helps in maintaining the mucosal integrity  NH3 + Glutamic acid > Glutamine Bifidobacteria

 Saccharomyeces:  Boullardii,  Salivarium,  Thermophilus  Non colonising yeast – so needs repeated readministration  Action in large intestine 17

6. Must be of human origin 3. Exert a beneficial effect on the host 1. Be nonpathogenic and nontoxic to the host 7. Contain a large number of viable cells and remain viable during storage and use 4.Capable of surviving, colonizing and proliferating in the gut (should not be killed by gastric juice / bile acids) 2. Be antagonistic to pathogens 5. Able to inhabit in the S & L intestine

 Bifidobacteria is an Important Probiotic as it maintains the mucosal integrity  Hence Bifidobacteria supplementation is useful in conditions like Gastroenteritis where the GI mucosa is severely damaged  However, all the marketed preparation contains only 1 – 3 species of Bifidobacteria as against 32 required  Hence it is ideal to supplement with probiotic which give nutrient to Bifidobacteria so all 32 species can proliferate

Non-digestible dietary supplements, which provide ‘’nutrition’’ for Probiotics Oligosaccharides (fructo-oligosaccharides or FOS), Inulin, Lactulose, Lactitol Mutated Bacterial Species (Streptococcus faecalis, Clostridium butyricum, Bacillus mesentericus) Advantage of Prebiotics in bacterial form : Addl. Probiotic activity ( Intrinsic Probiotic activity)

 Should promote the proliferation of beneficial bacteria (Lactiobaccillus, Bifidobacteria)  Supply nutrient to beneficial bacteria  Should escape digestion in the stomach and reach Intestine

ProbioticsPrebiotics Nature of the Prep Microorganism Food supplement (eg: FOS) or Microorganism (eg : S.F ) Prime FnTo kill harmful pathogen To supply nutrition (Killing the pathogen is an additional effect)

 FOS – Recommended daily dose is gm  Marketed prep. offer 100, 250 mg of FOS – Which is inadequate dose  Also at high dose, FOS cause flatulence and GI discomfort  Hence using a live mutated bacteria is beneficial as it would ensure the continuous colony count (nutrient) with out any side effect

1. Infective diarrhea (viral, bacterial) 2. Antibiotic associated diarrhea 3. Lactose intolerance 4. Recurrent aphthous ulcers and stomatitis 6. Inflammatory IBD (Ulcerative colitis, Crohn’s) 7. Irritable bowel syndrome 5. Travelers’ diarrhea 9. Pouchitis 8. Post operative state 10. Diverticular disease of colon

 Due to bacteria, Virus or Protozoa  Viral diarrhoea :  Rotavirus  Mx : ORS / Infusion  Bacterial Diarrhoea :  E.coli, Salmonella, Shigella, V. Cholerae  Mx : Antibacerial  Protozoal Diarrhoea :  E.Histolytics  Mx : Metrinadozole  An all the 3 types, there is a disturbance of the Intestinal microflora. Hence supplementation with Bifilac normalises the gut flora by displacing the PPMs and hence reduce the duration of diarrhoea

Bacteriocin Bioactive peptides Short chain fatty acids Neutralization of dietary carcinogens Neutralization of dietary carcinogens Free amino acids Organic acids β-Galactosidase activity Oligosaccharides Cholesterol assimilation Survival and adhesion competitions with pathogenic bacteria Survival and adhesion competitions with pathogenic bacteria Antioxidant Immunostimulatory Probiotics

L APC IgA Tumors Th 0 Th 1 B IL-2 ↑ IFN- γ ↑ Th 2 Antibody mediated response Cell mediated response Viruses TGF-β↓ IL-4 ↓ IL-10 ↓ + IL-2 ↑ IFN-γ ↑ TNF-α ↑ IFN-α ↑ Natural killer cells ↑ Macrophages ↑ Cytotoxic T-lymphocytes ↑ L L L Immune Response M Intestinal Epithelium Microorganisms B IgG ↑ IgM ↑ IgE ↓ Non-adhesive Adhesive M = M cells of intestinal epithelium L = Lymphocytes APC = Antigen presenting cells Th = T-helper cells IL = Interleukines TGF = Tumour growth factor IFN = Interferon TNF = Tumour necrosis factor Ig = Immunoglobulin

 Protection of intestinal epithelial barrier function  Regulation of intestinal epithelial homeostasis  Regulation of intestinal microbial environment  Modifications to commensal and probiotic bacteria to enhance diarrhea prevention

24  Most common antibiotics that cause diarrhea  Alteration in composition of normal intestinal bacterial micro flora by antibiotic makes the GI tract susceptible to infection by fungus (Candida) or bacteria, Clostridium difficile  Fungus alters absorptive surface of GI tract – diarrhea

31 Pseudomembranous Colitis Volcano lesions in AAD Relative risk of diarrhea reduced by 40 %. By LGG / Saccharomyces 5-10 billion viable organisms X 3-4 times/day Probiotics to be separated from Antibiotics by couple of Hours

The incidence of AAD can go up to 26% of patients on antibiotics, Broad-spectrum antibiotics are associated with the highest rate of AAD because of their disruptive impact on the normal intestinal flora. (2006) 3,

Diarrhea is a common adverse effect of antibiotic treatments. Antibiotic associated diarrhea occurs in about 5-30% of patients Almost all antibiotics, particularly those that act on anaerobes, can cause diarrhea, but the risk is higher with aminopenicillins, a combination of aminopenicillins and clavulanate, cephalosporin's, and clindamycin. BMJ 2002;324: (8 JUNE)

International Microbiology 2004 ; Mar 7(1) 59-62

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 Lactase digests lactose commonly present in milk and milk products.  Lactose is not digested when there is a deficiency in lactase and results in diarrhea.  Supplementation with probiotics has been shown to mitigate the symptoms of lactose intolerance.

 Superficial ulcers or fissures in mucosa of mouth.  Painful condition.  Each episode lasts days.  Exact etiology not known.  Stress appears to play a role.  Mx : B complex / multivitamin, probiotics and antiseptic or tetracycline mouth wash.

 Affects tourists traveling ; Shigella  Transmission of infection:  Feco-oral route / fingers and flies.  Travelers’ diarrhea can be prevented by regular prophylactic intake of beneficial bacteria  One week before travel, during travel, one week after completion of travel.

 Chronic medical condition characterized by abdominal pain, discomfort and results in change in the bowel frequency & consistency in the stools  Cause : Alteration in the bowel motility & transit ( due to anxiety)  Symptoms : Bloating, gas, dyspepsia, constipation, diarrhea, diarrhea alternating with constipation, dysentery

 Inflammation in GI Tract Crohn’s Disease Small & Large intestine Ulcerative Colitis Large intestine (Rectum & Colon) Ulcerative colitis Crohn’s disease

 Symptom : Diarrhoea / Dysentery / fever / Wt.loss  Rx : Sulphasalazine, Steroids, Immuno-suppresants  Rationale for Probiotic : IBD patients have a compromised bowel flora due to inflammation. Supplementation with probiotic helps to normalize the bowel flora and there by reduces the inflammation  Probiotics promotes the antigen specific IgA immune response and shortens the diarrheal phase. Also reduces the relapse rate

 Inflammation of an internal pouch created in patients who have part of their colon removed to treat ulcerative colitis  Why Probiotics : Low levels of bacterial flora in intestine

 Diverticula - Formation of small bulges / bags in the colon  Diverticulitis – Inflammation/ Infection in the diverticula

 Mixture of Pre and Probiotic  Probiotics – Helps in reducing the PPMs  Prebiotics – Helps in Providing food for Probiotics

 Lactobacillus sporogenes50 million ( Probiotic)  Streptococcus faecalis T million ( Prebiotic)  Clostridium butyricum TO-A2 million ( Prebiotic)  Bacillus mesentericus TO-A1 million ( Prebiotic)

 Streptococcus faecalis T million ( Prebiotic)  Clostridium butyricum TO-A2 million ( Prebiotic)  Bacillus mesentericus TO-A1 million ( Prebiotic)

Streptococcus faecalis ( Small ) Bacillus Mesentricus ( Small) Clostridium Butyricim ( Small & Large) On ingestion, 3 mutated live bacteria continue to proliferate in the GI tract by a process of Symbiosis Symbiosis : Biological association of two or more species to their mutual benefit.