Probiotics in health & diease

Probiotics in health & diease A Round Table Panel Discussion

Panelist: Each one of you

Scientific Co-ordinator: Dr.Mahesh Hiranandani

Armaan 6months / Boy

Ac.gastroenteritis Rx * ORS. * Danger signs explained.Masterly Inactivity

Monu 11 months /Boy

Acute bacillary Dysentry Rx. Stop milk. Stool R/E & Culture Syp Powergyl 2.5 ml BD Sporlac sachet 1TDS Zeedot sachet 1BD Zerolac formula. Kill them all

Priyanka 3yrs 3/11/08

Ac. Infective DiarrheaRx * Stool R/E. * Plenty of liquids. * Econorm sachets 1 BD * Stop milk. * Rice-dal, banana Curd, sooji & khichdi.

Balanced stroke

Acute Gastroenteritis Facts & Figures In developing countries overall burden is 6 to 12 episodes/year in under 5 age.

Mortality of 1.5 million children under 5.

Even USA spends 2 billion $/year on treatment of children with gastroenteritis.

ORS alone can cure most diarrheal episodes ???

No antibiotics..No ORSNo binding agents.No antimotility agents..

Then Is there any thing that will reduce the frequency & fluidity of stools ! ! !

How many of you believe in benefits of

PROBIOTICS

Probiotics: definition

World Health Organization: live microorganisms which when administered in adequate amounts confer a health benefit on the host

They:Survive stomach acid and bileEstablish residence in the intestinesImpart health benefits

Prebiotics (functional food)First identified in 1895Non-digestible food ingredients that stimulate the growth and/or activity of probioticsTypically oligosaccharides: galactooligosaccharides (GOS), fructo-OS (FOS), xylo-OS (XOS), InulinFound in: Breastmilk, Jerusalem artichoke, chicory root, raw dandelion greens, leeks, onions, garlic, asparagus, whole grains, beans, bananaAdding Prebiotics to Probiotics increases production of gut Short-Chain Fatty Acids (SCFA)

SynbioticsProducts containing BOTHPrebioticsProbiotics

Probiotic examplesLactobacillus sp.reutericaseiramnosusAcidophilusStreptococcus sp.Bifidobacterium sp.Infantis (breastmilk)lactislongumbrevebifidumSacharomyces boulardii Enterococcus spMixtures

Formulations: drops, chewable tablets, lozenges, capsules, straws, bottle capsBrands most often recommended by Pediatricians Sporlac Bifilac Econorm enterogermina Darolac Nutrolin B

Probiotic microorganisms

* Lactic acid producing bacteria Lactobacilli & Bifidobacterium * Yeast Saccharomyces boulardii * Others Bacillus ClausiiAll survive stomach acids & intestinal bileestablish in gut to impart health benefits.

Probiotics- normal source?

Colonization at birth with maternal speciesSpecific organisms vary by age in first yearBecome established by 1 yearDiet maternal milk, fermented milk, pickles, fermented soy (tempeh), etc. Successful probiotic treatment leads to temporary colonization

Initial Intentional Probiotic UseEli Metchnikoff - early 20th century (Russian Nobel laureate, professor at Pasteur Institute in Paris) ObservedBulgarians who drank milk fermented by lactic-acid producing bacteria had long livesLactic acid lowers gut pH and inhibits the growth of some pathogenic bacteria. Metchnikoff began drinking fermented milk and soon Parisian physicians did likewise.Henry Tissier at Pasteur Institute identified bacteria common in breastfed infant stool: BifidobacterLactobacillus acidophilus breaks down lactose and allows lactose intolerant individuals to drink milk

These are just a few

Composition of some of these Probiotic Preparation reminds of boring Microbiology lectures.

How many of us remember the actual beneficial strains ?

Mechanism of action Increases the number of beneficial bacteria and decreases the population of pathogens.

Competing with pathogens at mucosal sites.

Stimulating the mucosal immune mechanism.

Probiotics :Mechanism of action

Treatment of acute diarrhea Prevention of intestinal infections Inflammatory bowel disease Prevention of respiratory infections NNEC in preterm infants Treatment of AAC/AAD Prevention of atopy & other allergies. Treatment of constipation/ NN colic Hepatic encephalopathyProbiotics & Clinical Applications

Treatment of intestinal infectionsGold standard Rx for diarrhea remains ORS.

Probiotics are imporatant adjuvants.

Wide range of strains,dose,schedule & conditions.

Outcome studied : Duration, fluidity, hosp stay.

Bacteria Lactobacillus rhamnosus GG Lactobacillus reuteri Lactobacillus casei Lactobacillus acidophilus Bifidobacterium breve Enterococcus Yeasts Saccharomyces boulardii Others Bacillus clausiiProbiotics tested for use in diarrhea

Probiotics: infectious diarrheaTreatment: Systematic review > 9 studies in 1-36 month old children; significant reduction in diarrhea days (0.7, 95% CI: 0.3-1.2) and fewer stools with L GG (95% CI: 0.7-2.6); Dose response curve with higher L GG dose . Effects on Viral GE more convincing Van Niel et al. Pediatrics, 2002Allen et al. Cochrane Database Syst Rev, 2004

Meta-analysis of RCTs LGG reduced duration of diarrhea caused by Rotavirus Reduced the risk of persistent diarrhea Shortened the duration of hospitalization. Most effective at doses of 10 billion & above. More effective when given early in course Szajeewska et al Aliment phar ther 2007

Which strain is better.Meta-analysis of 5 RCTs S.Boulardii exerts moderate clinical benefit by reducing duration of diarrhea & risk of persistent diarrhea. Szajeweska et al .Ali phar ther 2007

Head to head comparative trial of different strains LGG Most effective in reducing duration & severity S.Boulardii No effect L.bulg,S.thermo Moderate improvement L.acid,B.bifi B.clausii No effect E.Faecium No effect Efficacy of probiotic is related to strain & dosage ( 10 billion cfu/day) Canani RB et al BMJ 2007

Probiotics: infectious diarrhea

Prevention: 2006 systematic review of 5 RCTs in day care and hospital settings: modest, but significant benefit for rotavirus or C. Diff. L GG, L reuteri > B lactis, Sach BoulardiGuandalini. J Clin Gastroenterol, 2006

Antibiotic-associated DiarrheaSystematic review of 9 placebo-controlled studies (2 in children) using various products: 60% reduction in incidence and duration of antibiotic associated diarrhea compared with placebo (P

Probiotics and infections1,018 pregnant mothers RCT mix (L rhamnosus GG and LC705, B breve Bb99, P freudenreichii) vs. placebo for 4 weeks before delivery; infants received same with or without GOS for 6 months.Two year follow-up no difference in neonatal morbidity, colic, or serious adverse effects; significantly fewer antibiotics prescribed to synbiotic group and fewer respiratory infectionsKukkonen K. Pediatrics, 2008

*Chemotherapy-associated diarrheaBenefits for pediatric oncology patients with diarrhea (incl C diff). Benchimol EI. J Pediatric Hematology/Oncology, 2004Breast cancer and colorectal cancer patients receiving chemotherapy had markedly less diarrhea with probiotics El-Atti S.Journal of Parenteral & Enteral Nutrition, 2009; Osterlund P. Br J Cancer, 2007Radiation induced diarrhea attenuated with probiotics. Delia P.Tumori, 2007; Fuccio L. J Clin Gastroenterol, 2009; Giralt J. Intl J Rad Onc Bio Physics, 2008

Probiotics: Respiratory IllnessWeizman, et al. 12 weeks of B lactis or L reuteri vs. controlsSignificant reductions, all favoring L reuteri inDays with fever (0.17 vs. 0.8, P

Probiotics: NEC prevention Meta-analysis of 9 trials randomizing 1,425 premature infants (

Preventive role of probiotics in NEC Meta analysis of 27 RCTs , 6655 preterm babiesOutcome studied Prevention of Bell stage 1 & 2 Significant redu Reduction in mortality Significant all causes Reduction in sepsis No sign risk for sepsis/deathConclusion Regardless of Gestational age or NEC stage probiotics reduce the incidence of NEC and also donot increase risk of sepsis or death. Yang et al 2014

Probiotics for Premature Infants: widespread implementation?What about < 1000 gram infants?11 studies used 10 different probioticsWhich strains? Combinations?What dose?Should strain and dose depend on type of milk feeding?Contraindications? (case report toxicity)Routine vs. informed consent?Soll RF. Pediatrics, 2010 (editorial)

Probiotics: colicRCT of L reuteri vs. simethicone for 28 days in 83 breast-fed infants Daily median crying timeDay 7 P:159 minutes vs S: 177 minutesDay 28 P: 51 minutes vs S: 145 minutes (P

Probiotics: EczemaProbiotic supplements for Finnish pregnant moms with 1st degree fam hx atopy: L GG 10 bill cfus daily for 2-4 weeks before delivery, followed by infants daily for 6 months. At 2 years old, eczema prevalence reduced from 46% to 23% (RR 0.51, CI: 0.32-0.84) Kalliomaki et al. Lancet 2001; Lancet, 2003; J Allergy Clin Immunol, 2007

Dutch RdbPCT (B. bifidum, B. lactis, and L. lactis) was given to pregnant women and to babies for first 12 months. Decreased risk of eczema with active treatment at 3 months, 6/50 vs 15/52 (P = 0.035) and at 12 months 23/50 vs 31/48.Niers L. Allergy, 2009

Probiotics: constipationMeta-analysis of 5 RCTs (3 adults n = 266; ) 2 children, n = 111). In adults, data suggest favorable effects of several probiotics. In children, L. casei rhamnosus Lcr35, but not L. rhamnosus GG, showed a beneficial effect.Chmielewska A. World J Gastroenterol, 2010

Every possible pro-prebiotic combo

Probiotics: prescribingWhich organism to use?S boulardii, Lactobacillus, and E faecium have prevented antibiotic-associated diarrheaL GG and L reuterii reduced infectious diarrhea L GG for eczemaL reuteri for colicWhich product? What dose? How long?Side effects? Cost?

Suitable Description of a Probiotic * Genus & species identification. * Strain designation. * Viable count at the end of shelf life. * Recommended storage condition. * Recommended dose. * Actual description of physiological effects.

Probiotics : Common myths* Do all Probiotic strains confer health benefits Not actually..Strain/dose specific relationship between the two.* If some dose is good..is more the better ? More is not actually better.one must stick to dose recommended by various bodies

Would you like to share your experience of Probiotics in treatment of diarrhea ?

ESPGHAN & ESPID position statements 2008

Probiotics may be an effective adjunct to themanagement of diarrhoea. However because there is no evidence of efficacy for many preparations , we suggest the use of probiotic Strains with proven efficacy & in appropriate doses for the management of Acute diarrhea as anadjunct to rehydration therapy . Lactobacillus GG & S boulardi were the only strains with proven efficacy.

NSG of

Have you taken your Probiotic today ?

Its not the red army but probioticsbeating pathogens black & blue

Check to see that the right strain is there in the right number.

PROBIOTICS

MARKET POTENTIAL

HEALTH CLAIM

JUSTIFICATION

Genera , species and strainsHealth benefits of probiotics are strain sp.No cross strain benefits.Benefits are dose & vehicle dependent.

Probiotic strain is listed by Genus..species ..Alphanumeric designation

Lactobacillus casei DN-114001 or Lactobacillus Rhamnosus GG

Probiotic safetyCase reports of bacteremia, fungemia, endocarditis, meningitis in immunocompromised children on ventilators2% bloating, gas, diarrheaIncreased allergic sensitization?

Food is safer than pills!

Suggested Practice ChangesRecommend L. acidophilus for patients with lactose intolerance For the next 30 days, recommend probiotics for outpatients who receive a prescription for antibiotics; monitor rate of diarrhea as a side effectTry different probiotic products yourself and monitor your own gut reactionRecommend probiotics (L GG) for patients with infectious diarrhea.Talk with your local neonatologist about using probiotics to help reduce risk of NEC.In the next week, talk with one mother of an infant about probiotics to help with colic.Prepare a comparative chart for various probiotic preparation & their clinical efficacy

Probiotics brands in IndiaSingle strain * Tab Sporolac L.sporogens 60 million * Cap Rexflora L.sporogens 180 million * Econorm Stibs/G norm S.Boulardii 250mg 10 billion cfu * Megaflora S.Boulardii 5 billion cfu * Enterogermina Tuffpro B.Clausii 200mill spores Multi strainBifilac L.sporo 50 million Flora SB Lacto rham /Acid 150mgLactisyn L.lactis /acido/ 1 billionEugi L acid/Rhamno 500 millionBiogut L.acid/rhamno 600 millionBifilin L acid/rhamno 1 billionBinifit Strep feca 30 mill/Clost butEcoflora L rhamno Gr 1 billionBeneflora L rhamno RR 2 billion

Take home pointsGood evidence for:Infectious diarrhea, txAntibx-assoc diarrheaNEC; premature mortality

Promising evidence for:Preventiong atopic conditionsConstipation

In the future we may be using probiotics as we use antibiotics today: with specific strains used for certain clinical situations guided by controlled studies

PrescribingLactobacillus GG best studied to dateCombination products not well studied, but may work as well10 billion organisms/dKeep refrigerated (except Culturelle and BioGaia)Give in cool food/drink2% risk bloating/gas

Conclusion* Evaluation of effects of probiotics have progressed from Empiricism to science.* Probiotics are effective adjuvant in M/M of diarrhea . only probiotics strains of proven efficacy in appropriate doses is suggested.* Increase in probiotic use is linked to concept of naturality which fulfills the desire of patients to take medicines free from side effects which is so true for probiotics

Thanks for your participation

Suggested Practice ChangesRecommend L. acidophilus for patients with lactose intolerance For the next 30 days, recommend probiotics for outpatients who receive a prescription for antibiotics; monitor rate of diarrhea as a side effectTry different probiotic products yourself and monitor your own gut reactionRecommend probiotics (L GG) for patients with infectious diarrhea.Talk with your local neonatologist about using probiotics to help reduce risk of NEC.In the next week, talk with one mother of an infant about probiotics to help with colic.Ask your hospital library to subscribe to ConsumerLab.com. Prepare a handout comparing different probiotic products for your patients.Join the AAP SOCIM: www.aap.org/sections/chim/

Probiotics: whats in yogurt?

ProductActiviaBreyers 99% Fat Free Fruit on the BottomDanActiveStonyfield Farm French Vanilla Nonfat YogurtYoPlusTypeB regularis (animalis, DN-173 010)L acidophilus? othersL casei Immunitatis (casei, DN-114 001)Bifidus L acidophilus, casei, bulgaricus, reuteriB. Lactis Bb-12 + inulin

Probiotics- normal source?

Colonization at birth with maternal speciesSpecific organisms vary by age in first yearBecome established by 1 yearDiet maternal milk, fermented milk, pickles, fermented soy (tempeh), etc. Successful probiotic treatment leads to temporary colonization

Probiotics: colicRCT of L reuteri vs. simethicone for 28 days in 83 breast-fed infants Daily median crying timeDay 7 P:159 minutes vs S: 177 minutesDay 28 P: 51 minutes vs S: 145 minutes (P

Probiotics: prescribingWhich organism to use?S boulardii, Lactobacillus, and E faecium have prevented antibiotic-associated diarrheaL GG and L reuterii reduced infectious diarrhea L GG for eczemaL reuteri for colicWhich product? What dose? How long?Side effects? Cost?

*Probiotics: product variability2004 Can Fam Physician (Huff BA) found 0/10 brands tested matched microbiologic specifications on label; typically, 0-10% of label quantities, often not including any of stated bacteria1996 BMJ (Hamilton-Miller JM) only 2/13 study of 13 British brands contained quantity of cfu listed on label

SynbioticsProducts containing BOTHPrebioticsProbiotics

* Decreased risks in adultsRecurrent colon and bladder cancer with probiotics/synbiotics; implications for pediatrics? Perioperative infections in abdominal surgery with probiotics in adults.

Implications for pediatrics

NNEC in preterm infants RCTs have confirmed reduced risk of NEC in preterm babies & lower mortality. Lactose malabsorption S.Thermophilus & L. bulgaricus improves lactose digestion & reduces sypmtoms. Hepatic encephalopathy Lactulose with synbiotics reverses HE. Allergy Strong evidence for prevention of atopy.

*Nosocomial infectionsL GG to prevent nosocomial GI and Respiratory infectionsRdbpCT, N=742 hospitalized children Dose L GG 109 daily in 100 ml fermented milkRRisk of GI infections 0.4 for LGG vs. placebo; NNT 15; (vomiting RR 0.3; diarrhea RR 0.24)RRisk of Respiratory infections 0.38 for LGG v placebo, NNT 30Hojsak I. , et alPediatrics, 2010 (May)

Probiotics and Evidence

What are the clinical conditions in which Probiotic administration is of proven beneficial outcome ?..

Probiotics: proposed mechanisms

Adherence and subsequent stimulation of gut immune systemUp-regulation of mucin geneEnhance secretory IgAMaintain normal macrophage functionCompetition for essential nutrientsProduction of antimicrobial factorsProvide favorable environment for growth of other beneficial bacteriaProduction of short-chain fatty acids with anti-inflammatory properties

* Probiotics reduce all-cause mortality and NECA systematic review, of 11 randomized, controlled trials (RCTs) in 2176 infants of

Its not the red army but probioticsbeating pathogens black & blue

Have you taken your Probiotic today ?

NSG of

Check to see that the right strain is there in the right number.

Probiotics: product variabilityConsumerLab.com tested 25 probiotic products19 for general population, 3 for children, 3 yogurts8 claimed a specific number of organisms per serving13 claimed only a number of organisms at time of manufacture8/25 contained less than 1 percent of the claimed number of live bacteria or of the expected minimum of 1 billion.7 of the 8 that gave expected numbers per serving met those countsNone contaminated with bacteria, mold, or fungusAll enteric-coated capsules passed testing

Probiotics: recommending

Lactobacillus rhamnosus GG, reuterii, best studied to dateCombination products not well studied, but may work as wellTypical effective dose: 10 billion organisms/dMost require refrigeration Can give in cool food/drink

Probiotics Living organisms which upon ingestion in sufficient numbers , exert health benefits beyond basic nutrition. Prebiotics Nondigestible oligosaccharides food that stimulates the growth of beneficial microorganisms already present in colon. Synbiotic Probiotic & prebiotic mixed together.

Primary Pediatric Uses of ProbioticsManage lactose intolerance (L acidophilus)Antibiotic-associated diarrhea and infectious diarrheaDecrease constipationDecrease risk of NEC and all cause mortality in premature infantsDecrease dental cariesTreatment of H pylorii infections, UTIDecrease colicDecrease risk of developing eczemaDecrease upper respiratory tract infections

Health & Medicine

Probiotics in health & diease