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 flora

Fermentation of dietary waste and endogenous mucins

Energy recovery through the generation of short-chain fatty acids

Protection against colonization and invasion by pathogens (barrier effect)

Development, stimulation and modulation of the immune system

Gut flora

By the age of two years, the flora established is practically definitive

Every individual tends to have a relatively stable flora

Negative modification by antibiotics

Positive modification by probiotics

Probiotics

Probiotics are living microorganisms that are consumed in order to obtain a beneficial effect regardless of their intrinsic nutritional value

Probiotics - criteria

Application in the living state

Resistance to gastric acid and bile

Ability to adhere to colonocytes

Ability to colonize the gut

Clinically proved favourable health-effect

Safety

Probiotics - effects

Involvement in production of essential nutrients of the colonic mucosa

Beneficial effect on intestinal immunity

Recovery of the disturbed gut mucosal barrier and prevention of microbial translocation

Elimination of toxins and eradication of microbial pathogens

Probiotics - effects

Competitive inhibitor of bacterial

adhesion

Synthesis of compounds that inhibit or

destroy pathogens

Competitive consumption of nutrients

required for growth of pathogens

Probiotics and clinical usage

Benefits are of varying degree dependent on :Number of agentsThe doseDosing patterns The characteristics of the hostUnderlying luminal microbial environment of the host

Saavedra JM

Probiotics - uses

Traveler’s diarrhoea

Antibiotic-associated diarrhoea

Relapsing Clostridium difficile colitis

Infantile diarrhoea

Rotavirus enteritis

Inflammatory bowel disease

Irritable bowel syndrome

Colon cancer

Probiotics - uses

Peritonitis

Acute pancreatitis

Diarrhoea associated with HIV infection

Probiotic agents with clinical dataLactobacillus 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

product

Vary greatly from one species to

another in genetic make up,

colonization and adherence patterns

Term “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 - Constipation

IMPROVED 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 DIARRHEA

EXAMPLE OF SINGLE STRAIN CONCEPT TO JUSTIFY STRAIN SPECIFICITY

Saccharomyces boularidii (Sb)

Non pathogenic thermophyilic yeast

Reaches high levels in stools in 3 – 5 days

Undetectable by 2 - 6 days after discontinuation

Sb - anti toxin effects

Prevention of cytotoxicity of toxins A and B of C. difficile

Reduces toxins A receptor binding

Neutralisation of cholera toxin

Neutralisation of heat stable enterotoxin of E. coli

Sb and C. difficile enteropathy

Prevention of recurrence

Surawicz

Prevention of recurrence in those who failed to respond to vancomycin and metronidazole

McFarland

Sb and antibiotic associated diarrhoea (AAD)

Prophylactic use of Sb with beta

lactam resulted in reduction of AAD

McFarland

Sb reduces the incidence of AAD in

hospitalized patients

Surawicz

Efficiency in preventing AAD 56%

McFarland

Sb - clinical uses

Nasogastric alimentation associated

diarrhoea

decrease in number of diarrhoeal days

HIV associated diarrhoea

decrease in stool frequency

Sb - clinical uses

Crohn’s disease

decreased frequency of bowel

movements

Traveler’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 Raised

1. Lack of sufficient evidence from South Asian countries regarding possible benefit of probiotic supplementation in humans.

2. 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.

3. The possible benefit from a probiotic preparation is dependent on specificity of the strain as well as host response and these may differ in the two settings.

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SUMMARY OF TRIALS(RCT)S. NO

CLINICAL SETTING PROBIOTIC STRAIN(S) PURPOSE RESULT

1. Acute watery diarrhea L. acidophilus Treatment No benefit

2. Acute watery diarrhea L. rhamnosus GG Treatment No benefit

3. Persistent diarrhea L.rhamnosus GG Treatment Benefit

4. Acute diarrhea L .casei DN-11400, L. bulgaricus, S. thermophilus, Lactococcus lactis, Lactococcus lactis cremoris, Leuconostamesenteroides cremoris

Treatment

+

PreventionBenefit

5. Morbidity B. Lactis(DR-10) Prevention Benefit

6. Neonatal sepsis L. plantarum Treatment Benefit

7. Ulcerative Colitis VSL#3 Treatment Benefit

8. Pediatric Irritable Bowel Syndrome

VSL#3 Treatment Benefit

9. Acute diarrhea L. casei Shirota Prevention Benefit

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Guidelines for the treatment of gastroenteritis by ESPGHANGuidelines for the treatment of gastroenteritis by ESPGHANGuarino & al. JPGN 2008;46:619-21Guarino & al. JPGN 2008;46:619-21

Guidelines for the treatment of gastroenteritis by ESPGHANGuidelines for the treatment of gastroenteritis by ESPGHANGuarino & al. JPGN 2008;46:619-21Guarino & al. JPGN 2008;46:619-21

S. BoulardiiS. Boulardii is acknowledged is acknowledged as an evidence-based probiotic as an evidence-based probiotic

and recommended by the ESPGHANand recommended by the ESPGHAN

“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).”

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 M

PASSAGE OF HARD STOOLS WITH DIFFICULTY - 2 YRS

IRREGULAR STOOL FREQUENCY - 2 YRS

Had 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.

Thank You