PROBIOTICS IN PEDIATRIC PRACTICE Dr Sarath Gopalan• Senior Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, PSRI Hospital, New Delhi.• Visiting Consultant in Pediatric Gastroenterology and Hepatology, Indraprastha Apollo Hospital, New Delhi.• Executive Director, Centre for Research on Nutrition Support Systems, New Delhi.• Deputy Director, Nutrition Foundation of India, New Delhi.
Functions of gut floraFermentation of dietary waste and endogenous mucinsEnergy recovery through the generation of short-chain fatty acidsProtection against colonization and invasion by pathogens (barrier effect)Development, stimulation and modulation of the immune system
Gut floraBy the age of two years, the flora established is practically definitiveEvery individual tends to have a relatively stable floraNegative modification by antibioticsPositive modification by probiotics
ProbioticsProbiotics are living microorganisms thatare consumed in order to obtain a beneficialeffect regardless of their intrinsic nutritionalvalue
Probiotics - criteriaApplication in the living stateResistance to gastric acid and bileAbility to adhere to colonocytesAbility to colonize the gutClinically proved favourable health-effectSafety
Probiotics - effectsInvolvement in production of essential nutrients of the colonic mucosaBeneficial effect on intestinal immunityRecovery of the disturbed gut mucosal barrier and prevention of microbial translocationElimination of toxins and eradication of microbial pathogens
Probiotics - effectsCompetitive inhibitor of bacterial adhesionSynthesis of compounds that inhibit or destroy pathogensCompetitive consumption of nutrients required for growth of pathogens
Probiotics and clinical usageBenefits are of varying degree dependent on : Number of agents The dose Dosing patterns The characteristics of the host Underlying luminal microbial environment of the host
Probiotics - usesPeritonitisAcute pancreatitisDiarrhoea associated with HIV infection
Probiotic agents with clinical data Lactobacillus GG Lactobacillus acidophilus Lactobacillus plantarum 299V Lactobacillus casei Shirota Bifidobacterium bifidum Bifidobacterium longam Streptococus thermophilus Enterococcus faecium SF68 Saccharomyces boulardii Bacillus clausii
LactobacillusLactobacillus is part of lactic acid bacteria - non pathogenic gram positive bacteria that produce lactic acid as a primary metabolic end productVary greatly from one species to another in genetic make up, colonization and adherence patternsTerm “lactobacillus” is meaningless
Lactobacillus casei – documented benefit• Recurrence of superficial bladder cancer (Urol Int 1992; 49:125-129, Urol Int 2002;68:273-280)• Significant improvement in sodium absorption in short bowel syndrome (JPGN April 2001;32:506-508)
L. Casei Shirota - ConstipationIMPROVED FREQUENCY AND < GI SYMPTOMS• Koebnick et al, Can J Gastroenterol 2003, Vol 17:11• Bioscience Microflora 2006; 25 (2):39 – 48• Chimielewska et al, World J Gastroenterol 2010; 16 (1) : 69 – 75• Krammer HJ, Coloproctology 2011; 33:109-113
Bacillus clausii•ACUTE DIARRHEA•ANTIBIOTIC – ASSOCIATED DIARRHEA•TRAVELLER’S DIARRHEAEXAMPLE OF SINGLE STRAIN CONCEPT TOJUSTIFY STRAIN SPECIFICITY
Saccharomyces boularidii (Sb)Non pathogenic thermophyilic yeastReaches high levels in stools in 3 – 5 daysUndetectable by 2 - 6 days after discontinuation
Sb - anti toxin effectsPrevention of cytotoxicity of toxins A andB of C. difficileReduces toxins A receptor bindingNeutralisation of cholera toxinNeutralisation of heat stable enterotoxinof E. coli
Sb and C. difficile enteropathyPrevention of recurrence SurawiczPrevention of recurrence in those whofailed to respond to vancomycin andmetronidazole McFarland
Sb and antibiotic associated diarrhoea (AAD)Prophylactic use of Sb with beta lactam resulted in reduction of AAD McFarlandSb reduces the incidence of AAD in hospitalized patients SurawiczEfficiency in preventing AAD 56% McFarland
Sb - clinical usesNasogastric alimentation associateddiarrhoea decrease in number of diarrhoeal daysHIV associated diarrhoea decrease in stool frequency
Sb - clinical usesCrohn’s disease decreased frequency of bowel movementsTraveler’s diarrhoea reduction in the incidence of diarrhoea
Single probiotic or cocktail??!!Rationale for using a probiotic “cocktail”- the beneficial effects of different probiotic agents may be additive – but is it really so?Advantage of using a single strain – easy to study the desired therapeutic effect and interpret it as responsible for the observed benefit.
Probiotic Supplementation in Developing Countries of South Asia• Issues Raised2. Lack of sufficient evidence from South Asian countries regarding possible benefit of probiotic supplementation in humans.3. It is likely that microbial colonization of the gut in individuals from countries like India who are exposed to a microbiologically hostile environment is considerably different from those in the developed countries of the West.4. The possible benefit from a probiotic preparation is dependent on specificity of the strain as well as host 23 response and these may differ in the two settings.
SUMMARY OF TRIALS(RCT)S. CLINICAL SETTING PROBIOTIC STRAIN(S) PURPOSE RESULTNO1. Acute watery diarrhea L. acidophilus Treatment No benefit2. Acute watery diarrhea L. rhamnosus GG Treatment No benefit3. Persistent diarrhea L.rhamnosus GG Treatment Benefit4. Acute diarrhea L .casei DN-11400, L. Treatment bulgaricus, S. thermophilus, Lactococcus lactis, + Lactococcus lactis cremoris, Leuconosta Benefit mesenteroides cremoris Prevention5. Morbidity B. Lactis(DR-10) Prevention Benefit6. Neonatal sepsis L. plantarum Treatment Benefit7. Ulcerative Colitis VSL#3 Treatment Benefit8. Pediatric Irritable Bowel VSL#3 Treatment Benefit Syndrome9. Acute diarrhea L. casei Shirota Prevention Benefit 24
Guidelines for the treatment of gastroenteritis by ESPGHANGuarino & al. JPGN 2008;46:619-21 “Probiotics may be an effective adjunct to the management of diarrhea. However, because there is no evidence of efficacy for many preparations, we suggest the use of Probiotic strains with proven efficacy and in appropriate doses for the management of children with AGE as an adjunct to rehydration therapy (II, B). The following Probiotics showed benefit in meta-analyses of clinical trials: Lactobacillus GG (I, A) and S.boulardii (I, A). Evidence of lack of risk of antibiotic resistance transfer is required for Probiotics proposed for clinical use (Vb, D).” S. Boulardii is acknowledged as an evidence-based probiotic and recommended by the ESPGHAN
LASPGHAN Guidelines(Latin American Society of Pediatric Gastroenterology ,Hepatology and Nutrition) Only S.boulardii & L.GG has been give 1A grade level of evidence
PEDIATRIC CASE STUDIES – L. casei Shirota N 3 YRS F RECURRENT LOOSE STOOLS - FOR 18 MONTHS Given antibiotics for 3 – 5 days on most occasions, loose stools subsided, but frequent recurrence. L. casei Shirota consumed once daily ( 65 ML) for 5 months ( irrespective of occurrence of loose stools) – parents observed decreased frequency of episodes of loose stools.
PEDIATRIC CASE STUDIES – (L.casei Shirota)- contd.. S 6 YRS MPASSAGE OF HARD STOOLS WITH DIFFICULTY - 2 YRSIRREGULAR STOOL FREQUENCY - 2 YRSHad received lactulose and cremaffin intermittently – no significant benefit.Then, received continuous medical treatment for 6 months as follows:-• LACTULOSE 15 ML TWICE DAILY ( AFTER LUNCH & DINNER), MON – SAT, 6 DAYS / WEEK.• POLYETHLENE GLYCOL ½ PACKET ONCE WEEKLY (EVERY SUNDAY) DISSOLVED IN TOTAL 1000 ML (600 ML BISLERI WATER + 400 ML MANGO FROOTI JUICE) OVER 3 HRS FOR 2 MONTHS, THEN STOPPED.• L. casei Shirota FOR 6 MONTHS AND STILL CONTINUING.• DISTINCT CLINICAL IMPROVEMENT - REGULAR STOOL PASSAGE ( 1 -2 / DAY), EASY.