More than 500 microbial species About 1 1,5 kg of our body weight 100,000,000,000,000 individual cells The GI tract is sterile in normal fetus Bacterial colonization Bifidobacteria Defense mechanism

BifidobacteriumLactobacillus EscherichiaGlostridiumStaphylococcusBacteriodesVeillonella

Friendly bacteria

Pathogenic bacteria

Opportunistic bacteria

Gut peristaltic Gastric acid Gut secretion ( bile, pancreatic juices, immonuglobulins ) Intestinal mucous Mucosal blood flow Enterocyte regeneration

Dietary componentsDigestion products

Intimate contact with immune system of gut( Gut Associated Lymphoid Tissue )

Ruthlein. 1992food + microorgansims = necessary for development ofGALT~25 40 % of the gut is lymphoid tissue

Up to 70% of all the immunecells are located in the instestine

Treatment of acute diarrhea Prevention of acute diarrhea Prevention of nosocomial diarrhea Treatment of Antibiotic Associated Diarrhea (AAD) Prevention of AAD

Randomized Clinical Trials Children with acute diarrhea Yogurt vs placebo Decrease duration of diarrhea

Isolauri et al ( 1994), Reza et al ( 1995 ), Pant et al ( 1995 )

RCT of Probiotic for treatment ofacute diarrhea

PROBIOTICAUTHORSNDAYTREATMENT GROUPCONTROL GROUPL rhamnosusIsolauri, 1991Raza, 1995Pant, 1996Shomikova, 1997Guandalini, 2000714026123287522551.4 days31% ( at day 2 )1.9 days2.7 days2.4 days2.4 days75% ( at day 2 )3.3 days3.7 days3.0 days

L reuteriShomikova, 1997Shomikova, 19976640551.5 days26% ( at day 2 )2.5 days81% ( at day 2 )S boulardiiCetina Sauri, 1989130415% ( at day 2 )60% ( at day 2 )

55 infants aged 5 24 months hospitalized for non- GI disease. Formula : Bifidobacteria vs control Observe for 7 months Diarrhea episode decreased ( 7 % vs 31 % ) Rotavirus enfection decreased ( 10 % vs 39 % )

Saavedra et al, 1994

ND is major problem in pediatric hospital worldwide 81 children aged 1 36 months hospitalized for reason other than diarrhea. RCT : LGG ( n = 45 ) vs placebo ( n = 36 ) LGG 6 x 109 cfu twice daily LGG reduced the risk of nosocomial diarrhea in comparison with placebo ( 6,7% vs 33,3 % ) LGG significantly reduced the risk of rotavirus gastroenteritis ( 2,2% vs 17,7 % )

Antibiotic associated diarrhea Metronidazole / vancomicyn Relapse Treatment with Lactobaillus casei Bacteria-produced substance inhibit in vitro the growth of enteropatogens, including C.difficille Prevent relapse of C difficille diarrhea

RCT of probiotic for prevention of antibiotic-associated diarrhea

PROBIOTICAUTHORSNDAYTREATMENT GROUP% DIARRHEACONTROL GROUP% DIARRHEAS boulardiiAdam, 1977Surawicz, 1989McFarland, 1995388180193728284.59.97.217.521.814.6L rhamnosusVanderhoof, 1999Arvoie, 19991881671030852616B longumOrrhage, 199420212070E faeciumWunderlich, 19894578.727.2

Helicobacter pylori Lactose intolerance Ulcerative colitis Necrotizing Enterocolitis

In vitro and in vivo data support the use of probiotics in Hp infections Adding probiotic to the standard tretment of Hp infections ( PPI and 2 antibiotics ) reduced side effects and improve compliances. Need more trials to replace current treatment on Hp infections

Children with lactose malabsorption ( BHT ) Milk, yogurt, pasteurized yogurt Administration of yogurt decrease H2 production and decrease symptom of lactose intolerance

Sherber et al, 1995 ; Montes et al, 1995

Pre and post test design, Jakarta 42/66 Junior High School students ( 12 -14 years old ) are lactose intolerance using BHT Full-cream milk for 1 week : all symptoms appeared : borborigmy, flatus, adbominal distention, nausea, vomiting, abdominal pain, and diarrhea. After 2 weeks of treatment with probiotic, 40 children free of symptoms Only 2 children still having abdominal distension and flatus

Boediarso et al, 2005

RCT in 18 patients of active UC Bifidobacterium longum + FOS (1 month) Clinical status, laboratory and biopsy Sigmoidescopy score reduced ( p < 0,05 ) mRNA levels for human beta defensins 2,3 and 4 reduced ( p < 0,05 ) TNF, interleucin 1 reduced ( p < 0,05 ) Reduced inflammation in biopsy specimen

Furrie et al, 2005

Reduced NEC in an infant study in 585 VLBW infants in 12 NICUs in Italy using Lactobacillus GG with historical controls ( Hoyots et al, 1999 ) Infants given probiotic were less likely than control infants to develop NEC; 1,4 % vs 2,8 %, not statiscally significant ( Dani et al, 2002 )

A double blind, placebo controlled, randomized trial.14 child care center, Israel. Healthy infants aged 4 10 months, 12 weeks feeding and observation. 201 infants : control 60, B lactis 73, L reuteri 68 Infants fed probiotic supplemented formula had fewer and shorter episodes of diarrhea. No effect on respiratory illnesses The effect more prominent with L reuteri

Weizman et al, 2005

RCT over 7 month To examine whether long term consumption or a probiotic milk could reduce respiratory infections in children in daycare centers. 18 daycare centers in Helsinki, Finland. 571 healthy children aged 1- 6 years, 282 in intervention group and 289 in the control group. Milk with our without Lactobacillus GG, 260 ml daily Lactobacillus reduce respiratory infections and their severity among children in daycare center. Hatakka et al, 2001

Competitive inhibition of bacterial adhesion Synthesis of compounds that inhibit or destroy pathogens Stimulation of immune response to pathogens Competitive consumption of nutrient required for growth of pathogens.

A recent review of 143 human clinical trials of probiotics between 1961 and 1998 involving more than 7500 subjects found no adverse events.

Epidemiologic links between less exposure to microbes and allergic disease, and protective effects of higher microbial burden.Intestinal microbiotica are the largest source of microbial exposure through early immune developmentIntestinal microbiotica appear to be essential for development of oral toleranceChanging patterns of microbiotica with progressive Westernization and links with allergic disease.Differences in perinatal colonization in children who go on to develop allergic diseasePerinatal administration of probiotics associated with anti-inflammatory and immunoregulatory effects on immune function.Presymptomatic immune dysregulation evident in infants and newborns who later develop allergic disease, suggesting that ellergy prevention should be initiated early.Initial studies with probiotics suggested promise in the prevention and early treatment of allergis disease.

Mengaktivasi makrofag untuk meningkatkan pemaparan antigen dengan limfosit B. Meningkatkan produksi secretory IgA baik secara lokal maupun sistemik Memodulasi sitokin

Sumber : WGO, 2008.19

Mencerna makanan dan kompetitif nutrisi terhadap patogen.Mempengaruhi PH lokal untuk membuat kondisi yang tidak menguntungkan untuk patogen.Memproduksi bakteriosin untuk menghambat patogen.Stimulasi produksi epithelial mucin.Memperkuat fungsi barrier intestinal.Kompetitif adhesi terhadap patogen.

Sumber : WGO.2008.19

Probiotics appear to be useful in the prevention or treatment of several gastrointestinal disorders, including infectious diarrhea, antibiotic associated diarrhea, nosocomial diarrhea , and lactose intolerance. Safety does not appera to be a sginificant concern. Research on probiotics in some diseases should be done to get more clinical evidences