A detailed ppt on history,types ,clinical applications ,efficacy of all probiotics

1. Probiotics in health & dieaseProbiotics in health & diease
A Round Table Panel DiscussionA Round Table Panel Discussion
Panelist: Each one of youPanelist: Each one of you
Scientific Co-ordinator: Dr.Mahesh HiranandaniScientific Co-ordinator: Dr.Mahesh Hiranandani

2. Armaan 6months / BoyArmaan 6months / Boy
Ac.gastroenteritisAc.gastroenteritis
RxRx
* ORS.* ORS.
* Danger signs explained.* Danger signs explained.
Masterly Inactivity

3. Monu 11 months /BoyMonu 11 months /Boy
Acute bacillary DysentryAcute bacillary Dysentry
Rx.Rx.
Stop milk.Stop milk.
Stool R/E & CultureStool R/E & Culture
Syp Powergyl 2.5 ml BDSyp Powergyl 2.5 ml BD
Sporlac sachet 1TDSSporlac sachet 1TDS
Zeedot sachet 1BDZeedot sachet 1BD
Zerolac formula.Zerolac formula.
Kill them allKill them all

4. Priyanka 3yrs 3/11/08Priyanka 3yrs 3/11/08
Ac. Infective DiarrheaAc. Infective Diarrhea
RxRx
* Stool R/E.* Stool R/E.
* Plenty of liquids.* Plenty of liquids.
* Econorm sachets 1 BD* Econorm sachets 1 BD
* Stop milk.* Stop milk.
* Rice-dal, banana* Rice-dal, banana
Curd, sooji & khichdi.Curd, sooji & khichdi.
Balanced strokeBalanced stroke

5. Acute Gastroenteritis – Facts &Acute Gastroenteritis – Facts &
FiguresFigures
In developing countries overall burdenIn developing countries overall burden
is 6 to 12 episodes/year in under 5 age.is 6 to 12 episodes/year in under 5 age.
Mortality of 1.5 million children under 5.Mortality of 1.5 million children under 5.
Even USA spends 2 billion $/year onEven USA spends 2 billion $/year on
treatment of children with gastroenteritis.treatment of children with gastroenteritis.

6. ORSORS
alonealone
cancan
curecure
mostmost
diarrhealdiarrheal
episodes ???episodes ???

7. No antibiotics…..No antibiotics…..
No ORS……No ORS……
No binding agents….No binding agents….
No antimotility agents…..No antimotility agents…..
Then Is there any thing that will reduce theThen Is there any thing that will reduce the
frequency & fluidity of stools ! ! !frequency & fluidity of stools ! ! !

8. How many of you believe in benefits ofHow many of you believe in benefits of
PROBIOTICSPROBIOTICS

9. ProProbiotics: definitionbiotics: definition
 World Health Organization:World Health Organization:
 ““live microorganisms which when administered inlive microorganisms which when administered in
adequate amounts confer a health benefit on theadequate amounts confer a health benefit on the
host”host”
 They:They:
 Survive stomach acid and bileSurvive stomach acid and bile
 Establish residence in the intestinesEstablish residence in the intestines
 Impart health benefitsImpart health benefits

10. PrePrebiotics (functional food)biotics (functional food)
 First identified in 1895First identified in 1895
 Non-digestibleNon-digestible food ingredients thatfood ingredients that
stimulate the growth and/or activity ofstimulate the growth and/or activity of
probioticsprobiotics
 Typically oligosaccharides:Typically oligosaccharides:
galactooligosaccharides (GOS), fructo-galactooligosaccharides (GOS), fructo-
OS (FOS), xylo-OS (XOS), InulinOS (FOS), xylo-OS (XOS), Inulin
 Found in: Breastmilk, JerusalemFound in: Breastmilk, Jerusalem
artichoke, chicory root, raw dandelionartichoke, chicory root, raw dandelion
greens, leeks, onions, garlic, asparagus,greens, leeks, onions, garlic, asparagus,
whole grains, beans, bananawhole grains, beans, banana
 Adding Prebiotics to Probiotics increasesAdding Prebiotics to Probiotics increases
production of gut Short-Chain Fatty Acidsproduction of gut Short-Chain Fatty Acids
(SCFA)(SCFA)

11. SynbioticsSynbiotics
Products containingProducts containing
BOTHBOTH
PrebioticsPrebiotics
ProbioticsProbiotics

12. Probiotic examplesProbiotic examples
 LactobacillusLactobacillus sp.sp.
 reuterireuteri
 caseicasei
 ramnosusramnosus
 AcidophilusAcidophilus
 StreptococcusStreptococcus sp.sp.
 BifidobacteriumBifidobacterium sp.sp.
 Infantis (breastmilk)Infantis (breastmilk)
 lactislactis
 longumlongum
 brevebreve
 bifidumbifidum
 Sacharomyces boulardiiSacharomyces boulardii
 EnterococcusEnterococcus spsp
 MixturesMixtures
 Formulations: drops, chewable tablets, lozenges, capsules, straws, bottle capsFormulations: drops, chewable tablets, lozenges, capsules, straws, bottle caps
 Brands most often recommended by Pediatricians Sporlac Bifilac EconormBrands most often recommended by Pediatricians Sporlac Bifilac Econorm
enterogermina Darolac Nutrolin Benterogermina Darolac Nutrolin B

13. Probiotic microorganismsProbiotic microorganisms
* Lactic acid producing bacteria* Lactic acid producing bacteria
Lactobacilli & BifidobacteriumLactobacilli & Bifidobacterium
* Yeast* Yeast
Saccharomyces boulardiiSaccharomyces boulardii
* Others* Others
Bacillus ClausiiBacillus Clausii
All survive stomach acids & intestinal bileAll survive stomach acids & intestinal bile
establish in gut to impart health benefits.establish in gut to impart health benefits.

14. Probiotics- normal source?Probiotics- normal source?
 Colonization at birth withColonization at birth with
maternal speciesmaternal species
 Specific organisms vary by ageSpecific organisms vary by age
in first yearin first year
 Become established by 1 yearBecome established by 1 year
 Diet – maternal milk, fermentedDiet – maternal milk, fermented
milk, pickles, fermented soymilk, pickles, fermented soy
(tempeh), etc.(tempeh), etc.
 ““Successful” probiotic treatmentSuccessful” probiotic treatment
leads to temporary colonizationleads to temporary colonization

15. Initial Intentional Probiotic UseInitial Intentional Probiotic Use
 Eli Metchnikoff - early 20Eli Metchnikoff - early 20thth
century (Russian Nobelcentury (Russian Nobel
laureate, professor at Pasteur Institute in Paris)laureate, professor at Pasteur Institute in Paris)
 ObservedObserved
 Bulgarians who drank milk fermented by lactic-acidBulgarians who drank milk fermented by lactic-acid
producing bacteria had long livesproducing bacteria had long lives
 Lactic acid lowers gut pH and inhibits the growth of someLactic acid lowers gut pH and inhibits the growth of some
pathogenic bacteria.pathogenic bacteria.
 Metchnikoff began drinking fermented milk and soonMetchnikoff began drinking fermented milk and soon
Parisian physicians did likewise.Parisian physicians did likewise.
 Henry Tissier at Pasteur Institute identified bacteriaHenry Tissier at Pasteur Institute identified bacteria
common in breastfed infant stool:common in breastfed infant stool: BifidobacterBifidobacter
 Lactobacillus acidophilusLactobacillus acidophilus breaks down lactose andbreaks down lactose and
allows lactose intolerant individuals to drink milkallows lactose intolerant individuals to drink milk

16. These are just a few……

17. Composition of some of these ProbioticComposition of some of these Probiotic
Preparation reminds of boring MicrobiologyPreparation reminds of boring Microbiology
lectures.lectures.
How many of us remember the actualHow many of us remember the actual
beneficial strains ?beneficial strains ?

18. Mechanism of actionMechanism of action
Increases the number of beneficial bacteriaIncreases the number of beneficial bacteria
and decreases the population of pathogens.and decreases the population of pathogens.
Competing with pathogens at mucosal sites.Competing with pathogens at mucosal sites.
Stimulating the mucosal immune mechanism.Stimulating the mucosal immune mechanism.

19. Probiotics :Mechanism of actionProbiotics :Mechanism of action

20. Treatment of acute diarrheaTreatment of acute diarrhea
Prevention of intestinal infectionsPrevention of intestinal infections
Inflammatory bowel diseaseInflammatory bowel disease
Prevention of respiratory infectionsPrevention of respiratory infections
NNEC in preterm infantsNNEC in preterm infants
Treatment of AAC/AADTreatment of AAC/AAD
Prevention of atopy & other allergies.Prevention of atopy & other allergies.
Treatment of constipation/ NN colicTreatment of constipation/ NN colic
Hepatic encephalopathyHepatic encephalopathy
Probiotics & Clinical ApplicationsProbiotics & Clinical Applications

21. Treatment of intestinal infectionsTreatment of intestinal infections
 Gold standard Rx for diarrhea remains ORS.Gold standard Rx for diarrhea remains ORS.
 Probiotics are imporatant adjuvants.Probiotics are imporatant adjuvants.
 Wide range of strains,dose,schedule & conditions.Wide range of strains,dose,schedule & conditions.
 Outcome studied : Duration, fluidity, hosp stay.Outcome studied : Duration, fluidity, hosp stay.

22. BacteriaBacteria
Lactobacillus rhamnosus GGLactobacillus rhamnosus GG
Lactobacillus reuteriLactobacillus reuteri
Lactobacillus casei Lactobacillus acidophilusLactobacillus casei Lactobacillus acidophilus
Bifidobacterium breveBifidobacterium breve
EnterococcusEnterococcus
YeastsYeasts
Saccharomyces boulardiiSaccharomyces boulardii
OthersOthers
Bacillus clausiiBacillus clausii
Probiotics tested for use in diarrheaProbiotics tested for use in diarrhea

23. Probiotics: infectious diarrheaProbiotics: infectious diarrhea
 Treatment:Treatment:
Systematic review > 9 studies in 1-36 month old children;Systematic review > 9 studies in 1-36 month old children;
significant reduction in diarrheasignificant reduction in diarrhea days (0.7, 95% CI: 0.3-1.2) anddays (0.7, 95% CI: 0.3-1.2) and
fewer stools withfewer stools with L GGL GG (95% CI: 0.7-2.6); Dose response curve(95% CI: 0.7-2.6); Dose response curve
with higherwith higher L GGL GG dose .dose . Effects on Viral GE more convincingEffects on Viral GE more convincing
Van Niel et al.Van Niel et al. Pediatrics,Pediatrics, 20022002
Allen et al.Allen et al. Cochrane Database Syst RevCochrane Database Syst Rev, 2004, 2004
Meta-analysis of RCT’sMeta-analysis of RCT’s
LGG reduced duration of diarrhea caused by RotavirusLGG reduced duration of diarrhea caused by Rotavirus
Reduced the risk of persistent diarrheaReduced the risk of persistent diarrhea
Shortened the duration of hospitalization.Shortened the duration of hospitalization.
Most effective at doses of 10 billion & above.Most effective at doses of 10 billion & above.
More effective when given early in courseMore effective when given early in course
Szajeewska et al Aliment phar ther 2007Szajeewska et al Aliment phar ther 2007

24. Which strain is better…….Which strain is better…….
 Meta-analysis of 5 RCT’sMeta-analysis of 5 RCT’s
S.BoulardiiS.Boulardii exerts moderate clinical benefit by reducing durationexerts moderate clinical benefit by reducing duration
of diarrhea & risk of persistent diarrhea.of diarrhea & risk of persistent diarrhea.
Szajeweska et al .Ali phar ther 2007Szajeweska et al .Ali phar ther 2007
• Head to head comparative trial of different strainsHead to head comparative trial of different strains
LGGLGG Most effective in reducing duration & severityMost effective in reducing duration & severity
S.BoulardiiS.Boulardii No effectNo effect
L.bulg,S.thermoL.bulg,S.thermo Moderate improvementModerate improvement
L.acid,B.bifiL.acid,B.bifi
B.clausiiB.clausii No effectNo effect
E.FaeciumE.Faecium No effectNo effect
Efficacy of probiotic is related to strain & dosage ( 10 billion cfu/day)Efficacy of probiotic is related to strain & dosage ( 10 billion cfu/day)
Canani RB et al BMJ 2007Canani RB et al BMJ 2007

25. Probiotics: infectious diarrheaProbiotics: infectious diarrhea
 PreventionPrevention::
2006 systematic review of 5 RCTs in day care and hospital2006 systematic review of 5 RCTs in day care and hospital
settings:settings: modest,modest, but significant benefit for rotavirus or C.but significant benefit for rotavirus or C.
Diff.Diff. L GGL GG,, L reuteri > B lactis, Sach BoulardiL reuteri > B lactis, Sach Boulardi
Guandalini.Guandalini. J Clin GastroenterolJ Clin Gastroenterol, 2006, 2006

27. Antibiotic-associated DiarrheaAntibiotic-associated Diarrhea
Systematic review of 9 placebo-controlled studies (2 inSystematic review of 9 placebo-controlled studies (2 in
children) using various products:children) using various products: 60% reduction60% reduction inin
incidence and duration of antibiotic associatedincidence and duration of antibiotic associated
diarrhea compared with placebo (P<0.01) 2002diarrhea compared with placebo (P<0.01) 2002
S.Boulardii & L.Rhanosus GGrS.Boulardii & L.Rhanosus GGr
9/10 pediatric trials (different products) favored9/10 pediatric trials (different products) favored
probiotics (probiotics (RR 0.49RR 0.49; 95% CI 0.32 to 0.74). None of; 95% CI 0.32 to 0.74). None of
the 5 trials monitoring adverse events (n = 647)the 5 trials monitoring adverse events (n = 647)
reported a serious adverse event.reported a serious adverse event.
Johnston BC.Johnston BC. Cochrane Database Syst RevCochrane Database Syst Rev, 2007, 2007
D’Souza et al.D’Souza et al. BMJ,BMJ, 20022002

28. Probiotics and infectionsProbiotics and infections
 1,018 pregnant mothers RCT mix (1,018 pregnant mothers RCT mix (LL
rhamnosus GGrhamnosus GG and LC705,and LC705, B breve Bb99, PB breve Bb99, P
freudenreichiifreudenreichii) vs. placebo for 4 weeks before) vs. placebo for 4 weeks before
delivery; infants received same with or withoutdelivery; infants received same with or without
GOS for 6 months.GOS for 6 months.
 Two year follow-up – no difference in neonatalTwo year follow-up – no difference in neonatal
morbidity, colic, or serious adverse effects;morbidity, colic, or serious adverse effects;
significantly fewer antibiotics prescribed tosignificantly fewer antibiotics prescribed to
synbiotic group and fewer respiratorysynbiotic group and fewer respiratory
infectionsinfections
Kukkonen K.Kukkonen K. PediatricsPediatrics, 2008, 2008

29. **Chemotherapy-associated diarrheaChemotherapy-associated diarrhea
 Benefits for pediatric oncology patients with diarrheaBenefits for pediatric oncology patients with diarrhea
(incl C diff).(incl C diff). Benchimol EI.Benchimol EI. J PediatricJ Pediatric
Hematology/OncologyHematology/Oncology, 2004, 2004
 Breast cancer and colorectal cancer patientsBreast cancer and colorectal cancer patients
receiving chemotherapy had markedly less diarrheareceiving chemotherapy had markedly less diarrhea
with probioticswith probiotics El-Atti S.El-Atti S.Journal of Parenteral &Journal of Parenteral &
Enteral Nutrition,Enteral Nutrition, 2009; Osterlund P.2009; Osterlund P. Br J CancerBr J Cancer,,
20072007
 Radiation induced diarrhea attenuated withRadiation induced diarrhea attenuated with
probiotics.probiotics. Delia P.Delia P.TumoriTumori, 2007; Fuccio L., 2007; Fuccio L. J ClinJ Clin
Gastroenterol,Gastroenterol, 2009; Giralt J2009; Giralt J. Intl J Rad Onc Bio. Intl J Rad Onc Bio
Physics,Physics, 20082008

30. Probiotics: Respiratory IllnessProbiotics: Respiratory Illness
Weizman, et al. 12 weeks ofWeizman, et al. 12 weeks of B lactisB lactis oror LL
reuterireuteri vs. controlsvs. controls
Significant reductions, all favoringSignificant reductions, all favoring L reuteriL reuteri
inin
Days with fever (0.17 vs. 0.8, P<0.001)Days with fever (0.17 vs. 0.8, P<0.001)
Episodes of fever (0.1 vs. 0.4, P<0.001)Episodes of fever (0.1 vs. 0.4, P<0.001)
Antibiotic prescriptions (0.06 vs. 0.19, P<0.05)Antibiotic prescriptions (0.06 vs. 0.19, P<0.05)
Weizman,Weizman, PediatricsPediatrics, 2005, 2005

31. Probiotics: NEC preventionProbiotics: NEC prevention
Meta-analysis of 9 trials randomizing 1,425Meta-analysis of 9 trials randomizing 1,425
premature infants (<37 weeks or < 2500 gms) topremature infants (<37 weeks or < 2500 gms) to
prophylactic probiotics, vs. placebo or ;prophylactic probiotics, vs. placebo or ;
probioticsprobiotics significantly reduced severe NECsignificantly reduced severe NEC byby
0.32 and0.32 and mortality by 0.43mortality by 0.43 (P<0.05); no impact(P<0.05); no impact
on nosocomial sepsis or length of TPN.on nosocomial sepsis or length of TPN.
SafetySafety: no observed cases of systemic infection: no observed cases of systemic infection
with the probiotic agents.with the probiotic agents.
More research needed in ELBW infants.More research needed in ELBW infants.
Alfaleh K.Alfaleh K. NeonatologyNeonatology, 2010, 2010

32. Preventive role of probiotics in NECPreventive role of probiotics in NEC
Meta analysis of 27 RCTs , 6655 preterm babiesMeta analysis of 27 RCTs , 6655 preterm babies
Outcome studiedOutcome studied
Prevention of Bell stage 1 & 2Prevention of Bell stage 1 & 2 Significant reduSignificant redu
Reduction in mortalityReduction in mortality Significant all causesSignificant all causes
Reduction in sepsisReduction in sepsis No sign risk for sepsis/deathNo sign risk for sepsis/death
ConclusionConclusion
Regardless of Gestational age or NEC stageRegardless of Gestational age or NEC stage
probiotics reduce the incidence of NEC and alsoprobiotics reduce the incidence of NEC and also
donot increase risk of sepsis or death.donot increase risk of sepsis or death. Yang et al 2014Yang et al 2014

34. Probiotics for Premature Infants:Probiotics for Premature Infants:
widespread implementation?widespread implementation?
 What about < 1000 gram infants?What about < 1000 gram infants?
 11 studies used 10 different probiotics11 studies used 10 different probiotics
 Which strains? Combinations?Which strains? Combinations?
 What dose?What dose?
 Should strain and dose depend on type ofShould strain and dose depend on type of
milk feeding?milk feeding?
 Contraindications? (case report toxicity)Contraindications? (case report toxicity)
 Routine vs. informed consent?Routine vs. informed consent?
Soll RF.Soll RF. PediatricsPediatrics, 2010 (editorial), 2010 (editorial)

35. Probiotics: colicProbiotics: colic
RCT ofRCT of L reuteriL reuteri vs. simethicone for 28vs. simethicone for 28
days in 83 breast-fed infantsdays in 83 breast-fed infants
Daily median crying timeDaily median crying time
Day 7 P:159 minutes vs S: 177 minutesDay 7 P:159 minutes vs S: 177 minutes
Day 28 P:Day 28 P: 51 minutes vs S: 145 minutes51 minutes vs S: 145 minutes
(P<0.01)(P<0.01)
Percent responders by 28 days:Percent responders by 28 days: 95% of95% of
Probiotic vs. 7% of simethiconeProbiotic vs. 7% of simethicone (P<0.01)(P<0.01)
No adverse effects reportedNo adverse effects reported
Savino F.Savino F. PediatricsPediatrics, 2007, 2007

36. Probiotics: EczemaProbiotics: Eczema
 Probiotic supplements for FinnishProbiotic supplements for Finnish pregnantpregnant moms with 1moms with 1stst
degree fam hx atopy:degree fam hx atopy: L GGL GG 10 bill cfu’s daily for 2-410 bill cfu’s daily for 2-4
weeks before delivery, followed by infants daily for 6weeks before delivery, followed by infants daily for 6
months. At 2 years old, eczema prevalence reduced frommonths. At 2 years old, eczema prevalence reduced from
46% to 23%46% to 23% ((RR 0.51RR 0.51, CI: 0.32-0.84), CI: 0.32-0.84)
Kalliomaki et al.Kalliomaki et al. LancetLancet 2001;2001; Lancet,Lancet, 2003;2003; J Allergy Clin ImmunolJ Allergy Clin Immunol, 2007, 2007
 Dutch RdbPCTDutch RdbPCT ((B. bifidum, B. lactisB. bifidum, B. lactis, and, and L. lactisL. lactis) was) was
given to pregnant women and to babies for first 12given to pregnant women and to babies for first 12
months. Decreased risk of eczema with active treatmentmonths. Decreased risk of eczema with active treatment
at 3 months,at 3 months, 6/50 vs 15/526/50 vs 15/52 (P = 0.035) and at 12 months(P = 0.035) and at 12 months
23/50 vs 31/48.23/50 vs 31/48.
Niers L.Niers L. AllergyAllergy, 2009, 2009

37. Probiotics: constipationProbiotics: constipation
Meta-analysis of 5 RCTs (3 adults n =Meta-analysis of 5 RCTs (3 adults n =
266; ) 2 children, n = 111). In adults, data266; ) 2 children, n = 111). In adults, data
suggest favorable effects of severalsuggest favorable effects of several
probiotics. In children,probiotics. In children, L. casei rhamnosusL. casei rhamnosus
Lcr35Lcr35, but not, but not L. rhamnosus GGL. rhamnosus GG, showed, showed
a beneficial effect.a beneficial effect.
Chmielewska A.Chmielewska A. World J GastroenterolWorld J Gastroenterol, 2010, 2010

38. Every possible pro-prebiotic combo

39. Probiotics: prescribingProbiotics: prescribing
Which organism to use?Which organism to use?
S boulardii, Lactobacillus, and E faecium haveS boulardii, Lactobacillus, and E faecium have
prevented antibiotic-associated diarrheaprevented antibiotic-associated diarrhea
L GG and L reuterii reduced infectiousL GG and L reuterii reduced infectious
diarrheadiarrhea
L GG for eczemaL GG for eczema
L reuteri for colicL reuteri for colic
Which product? What dose? How long?Which product? What dose? How long?
Side effects? Cost?Side effects? Cost?

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

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

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

43. ESPGHAN & ESPID position statementsESPGHAN & ESPID position statements
20082008
““ Probiotics may be an effective adjunct to theProbiotics may be an effective adjunct to the
management of diarrhoea. However becausemanagement of diarrhoea. However because
there is no evidence of efficacy for manythere is no evidence of efficacy for many
preparations , we suggest the use of probioticpreparations , we suggest the use of probiotic
Strains with proven efficacy & in appropriateStrains with proven efficacy & in appropriate
doses for the management of Acute diarrhea as andoses for the management of Acute diarrhea as an
adjunct to rehydration therapy . Lactobacillus GG &adjunct to rehydration therapy . Lactobacillus GG &
S boulardi were the only strains with proven efficacy.”S boulardi were the only strains with proven efficacy.”

44. NSG of

45. “Have you taken your Probiotic today” ?

46. Its not the red army but probiotics
beating pathogens black & blue

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

48. PROBIOTICS
MARKET POTENTIAL
HEALTH CLAIM
JUSTIFICATION

49. Genera , species and strainsGenera , species and strains
Health benefits of probiotics are strain sp.Health benefits of probiotics are strain sp.
No cross strain benefits.No cross strain benefits.
Benefits are dose & vehicle dependent.Benefits are dose & vehicle dependent.
Probiotic strain is listed by Genus..species ..Alphanumeric designationProbiotic strain is listed by Genus..species ..Alphanumeric designation
Lactobacillus casei DN-114001 or Lactobacillus Rhamnosus GGLactobacillus casei DN-114001 or Lactobacillus Rhamnosus GG

50. Probiotic safetyProbiotic safety
Case reports of bacteremia, fungemia,Case reports of bacteremia, fungemia,
endocarditis, meningitis inendocarditis, meningitis in
immunocompromised children onimmunocompromised children on
ventilatorsventilators
2% bloating, gas, diarrhea2% bloating, gas, diarrhea
Increased allergic sensitization?Increased allergic sensitization?
Food is safer than pills!Food is safer than pills!

51. Suggested Practice ChangesSuggested Practice Changes
 RecommendRecommend L. acidophilusL. acidophilus for patients with lactose intolerancefor patients with lactose intolerance
 For the next 30 days, recommend probiotics for outpatients whoFor the next 30 days, recommend probiotics for outpatients who
receive a prescription for antibiotics; monitor rate of diarrhea as areceive a prescription for antibiotics; monitor rate of diarrhea as a
side effectside effect
 Try different probiotic products yourself and monitor your own gutTry different probiotic products yourself and monitor your own gut
reactionreaction
 Recommend probiotics (L GG) for patients with infectious diarrhea.Recommend probiotics (L GG) for patients with infectious diarrhea.
 Talk with your local neonatologist about using probiotics to helpTalk with your local neonatologist about using probiotics to help
reduce risk of NEC.reduce risk of NEC.
 In the next week, talk with one mother of an infant about probioticsIn the next week, talk with one mother of an infant about probiotics
to help with colic.to help with colic.
 Prepare a comparative chart for various probiotic preparation & theirPrepare a comparative chart for various probiotic preparation & their
clinical efficacyclinical efficacy

52. Probiotics brands in IndiaProbiotics brands in India
 Single strainSingle strain
* Tab Sporolac L.sporogens 60 million* Tab Sporolac L.sporogens 60 million
* Cap Rexflora L.sporogens 180 million* Cap Rexflora L.sporogens 180 million
* Econorm* Econorm
Stibs/G norm S.Boulardii 250mgStibs/G norm S.Boulardii 250mg
10 billion cfu10 billion cfu
* Megaflora S.Boulardii 5 billion cfu* Megaflora S.Boulardii 5 billion cfu
* Enterogermina* Enterogermina
Tuffpro B.Clausii 200mill sporesTuffpro B.Clausii 200mill spores
Multi strainMulti strain
• Bifilac L.sporo 50 millionBifilac L.sporo 50 million
Flora SB Lacto rham /Acid 150mgFlora SB Lacto rham /Acid 150mg
• Lactisyn L.lactis /acido/ 1 billionLactisyn L.lactis /acido/ 1 billion
• Eugi L acid/Rhamno 500 millionEugi L acid/Rhamno 500 million
• Biogut L.acid/rhamno 600 millionBiogut L.acid/rhamno 600 million
• Bifilin L acid/rhamno 1 billionBifilin L acid/rhamno 1 billion
• Binifit Strep feca 30 mill/Clost butBinifit Strep feca 30 mill/Clost but
• Ecoflora L rhamno Gr 1 billionEcoflora L rhamno Gr 1 billion
• Beneflora L rhamno RR 2 billionBeneflora L rhamno RR 2 billion

53. Take home points…Take home points…
 Good evidence for:Good evidence for:
 Infectious diarrhea, txInfectious diarrhea, tx
 Antibx-assoc diarrheaAntibx-assoc diarrhea
 NEC; premature mortalityNEC; premature mortality
 Promising evidence for:Promising evidence for:
 Preventiong atopic conditionsPreventiong atopic conditions
 ConstipationConstipation
 In the future we may be usingIn the future we may be using
probiotics as we use antibioticsprobiotics as we use antibiotics
today: with specific strains usedtoday: with specific strains used
for certain clinical situationsfor certain clinical situations
guided by controlled studiesguided by controlled studies
 PrescribingPrescribing
 Lactobacillus GG bestLactobacillus GG best
studied to datestudied to date
 Combination productsCombination products
not well studied, but maynot well studied, but may
work as wellwork as well
 10 billion organisms/d10 billion organisms/d
 Keep refrigerated (exceptKeep refrigerated (except
Culturelle and BioGaia)Culturelle and BioGaia)
 Give in cool food/drinkGive in cool food/drink
 2% risk bloating/gas2% risk bloating/gas

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

55. Thanks for your
participation

56. Suggested Practice ChangesSuggested Practice Changes
 RecommendRecommend L. acidophilusL. acidophilus for patients with lactose intolerancefor patients with lactose intolerance
 For the next 30 days, recommend probiotics for outpatients whoFor the next 30 days, recommend probiotics for outpatients who
receive a prescription for antibiotics; monitor rate of diarrhea as areceive a prescription for antibiotics; monitor rate of diarrhea as a
side effectside effect
 Try different probiotic products yourself and monitor your own gutTry different probiotic products yourself and monitor your own gut
reactionreaction
 Recommend probiotics (L GG) for patients with infectious diarrhea.Recommend probiotics (L GG) for patients with infectious diarrhea.
 Talk with your local neonatologist about using probiotics to helpTalk with your local neonatologist about using probiotics to help
reduce risk of NEC.reduce risk of NEC.
 In the next week, talk with one mother of an infant about probioticsIn the next week, talk with one mother of an infant about probiotics
to help with colic.to help with colic.
 Ask your hospital library to subscribe to ConsumerLab.com. PrepareAsk your hospital library to subscribe to ConsumerLab.com. Prepare
a handout comparing different probiotic products for your patients.a handout comparing different probiotic products for your patients.
 Join the AAP SOCIM:Join the AAP SOCIM: www.www.aapaap.org/.org/sectionssections/chim//chim/

57. Probiotics: what’s in yogurt?Probiotics: what’s in yogurt?
Product Activia Breyers
99% Fat
Free Fruit
on the
Bottom…
DanActive Stonyfield
Farm
French
Vanilla
Nonfat
Yogurt
YoPlus
Type B
regularis
(animalis,
DN-173
010)
L
acidophilus
? others
L casei
Immunitatis
(casei, DN-
114 001)
Bifidus
L
acidophilus,
casei,
bulgaricus,
reuteri
B. Lactis
Bb-12 +
inulin

58. Probiotics- normal source?Probiotics- normal source?
 Colonization at birth withColonization at birth with
maternal speciesmaternal species
 Specific organisms vary by ageSpecific organisms vary by age
in first yearin first year
 Become established by 1 yearBecome established by 1 year
 Diet – maternal milk, fermentedDiet – maternal milk, fermented
milk, pickles, fermented soymilk, pickles, fermented soy
(tempeh), etc.(tempeh), etc.
 ““Successful” probiotic treatmentSuccessful” probiotic treatment
leads to temporary colonizationleads to temporary colonization

59. Probiotics: colicProbiotics: colic
RCT ofRCT of L reuteriL reuteri vs. simethicone for 28vs. simethicone for 28
days in 83 breast-fed infantsdays in 83 breast-fed infants
Daily median crying timeDaily median crying time
Day 7 P:159 minutes vs S: 177 minutesDay 7 P:159 minutes vs S: 177 minutes
Day 28 P:Day 28 P: 51 minutes vs S: 145 minutes51 minutes vs S: 145 minutes
(P<0.01)(P<0.01)
Percent responders by 28 days:Percent responders by 28 days: 95% of95% of
Probiotic vs. 7% of simethiconeProbiotic vs. 7% of simethicone (P<0.01)(P<0.01)
No adverse effects reportedNo adverse effects reported
Savino F.Savino F. PediatricsPediatrics, 2007, 2007

60. Probiotics: prescribingProbiotics: prescribing
Which organism to use?Which organism to use?
S boulardii, Lactobacillus, and E faecium haveS boulardii, Lactobacillus, and E faecium have
prevented antibiotic-associated diarrheaprevented antibiotic-associated diarrhea
L GG and L reuterii reduced infectiousL GG and L reuterii reduced infectious
diarrheadiarrhea
L GG for eczemaL GG for eczema
L reuteri for colicL reuteri for colic
Which product? What dose? How long?Which product? What dose? How long?
Side effects? Cost?Side effects? Cost?

61. **Probiotics: product variabilityProbiotics: product variability
 20042004 Can FamCan Fam
PhysicianPhysician (Huff BA)(Huff BA)
found 0/10 brandsfound 0/10 brands
tested matchedtested matched
microbiologicmicrobiologic
specifications onspecifications on
label; typically, 0-label; typically, 0-
10% of label10% of label
quantities, often notquantities, often not
including any ofincluding any of
stated bacteriastated bacteria
 1996 BMJ1996 BMJ
(Hamilton-Miller JM)(Hamilton-Miller JM)
only 2/13 study ofonly 2/13 study of
13 British brands13 British brands
contained quantitycontained quantity
of cfu listed on labelof cfu listed on label

62. SynbioticsSynbiotics
Products containingProducts containing
BOTHBOTH
PrebioticsPrebiotics
ProbioticsProbiotics

63. * Decreased risks in adults* Decreased risks in adults
 Recurrent colon and bladder cancerRecurrent colon and bladder cancer
with probiotics/synbiotics; implicationswith probiotics/synbiotics; implications
for pediatrics?for pediatrics?
 Perioperative infections in abdominalPerioperative infections in abdominal
surgery with probiotics in adults.surgery with probiotics in adults.
 Implications for pediatricsImplications for pediatrics

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

65. *Nosocomial infections*Nosocomial infections
L GG to prevent nosocomial GI andL GG to prevent nosocomial GI and
Respiratory infectionsRespiratory infections
RdbpCT, N=742 hospitalized childrenRdbpCT, N=742 hospitalized children
Dose L GG 10Dose L GG 1099
daily in 100 ml fermenteddaily in 100 ml fermented
milkmilk
RRisk of GI infectionsRRisk of GI infections 0.40.4 for LGG vs.for LGG vs.
placebo; NNT 15; (vomiting RR 0.3;placebo; NNT 15; (vomiting RR 0.3;
diarrhea RR 0.24)diarrhea RR 0.24)
RRisk of Respiratory infections 0.38 forRRisk of Respiratory infections 0.38 for
LGG v placebo, NNT 30

66. Probiotics and EvidenceProbiotics and Evidence
What are the clinical conditions in whichWhat are the clinical conditions in which
Probiotic administration is of provenProbiotic administration is of proven
beneficial outcome ?..beneficial outcome ?..

67. Copyright ©2010 American Academy of Pediatrics
Deshpande, G. et al. Pediatrics 2010;125:921-930
*FIGURE 4 Effect of probiotics on
all-cause mortality

68. Probiotics: proposed mechanismsProbiotics: proposed mechanisms
 Adherence and subsequent stimulation of gut immuneAdherence and subsequent stimulation of gut immune
systemsystem
 Up-regulation of mucin geneUp-regulation of mucin gene
 Enhance secretory IgAEnhance secretory IgA
 Maintain normal macrophage functionMaintain normal macrophage function
 Competition for essential nutrientsCompetition for essential nutrients
 Production of antimicrobial factorsProduction of antimicrobial factors
 Provide favorable environment for growth of otherProvide favorable environment for growth of other
beneficial bacteriabeneficial bacteria
 Production of short-chain fatty acids with anti-Production of short-chain fatty acids with anti-
inflammatory propertiesinflammatory properties

69. * Probiotics reduce all-cause* Probiotics reduce all-cause
mortality and NECmortality and NEC
““A systematic review, …of 11 randomized,A systematic review, …of 11 randomized, controlledcontrolled
trials (RCTs) in 2176 infants oftrials (RCTs) in 2176 infants of <34 weeks' gestation<34 weeks' gestation
revealed that oral probiotics reduced all-causerevealed that oral probiotics reduced all-cause
mortality andmortality and necrotizing enterocolitis (NEC) by morenecrotizing enterocolitis (NEC) by more
than half (than half (PP < .00001).”< .00001).” How?How?
 ““Probiotics upregulate local and system immunity,Probiotics upregulate local and system immunity,
increase anti-inflammatory cytokines and gutincrease anti-inflammatory cytokines and gut
impermeability to bacteria and toxins, and suppressimpermeability to bacteria and toxins, and suppress
pathogens associated with NEC.”pathogens associated with NEC.”
Tarnow-Mordi, et al.Tarnow-Mordi, et al. PediatricsPediatrics, 2010 (editorial), 2010 (editorial)
Soll RF.Soll RF. PediatricsPediatrics, 2010 (editorial), 2010 (editorial)
Deshpande G, et alDeshpande G, et al PediatricsPediatrics, 2010 (meta-analysis), 2010 (meta-analysis)

70. Its not the red army but probiotics
beating pathogens black & blue

71. “Have you taken your Probiotic today” ?

72. NSG of

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

74. Probiotics: product variabilityProbiotics: product variability
 ConsumerLab.com tested 25 probiotic productsConsumerLab.com tested 25 probiotic products
 19 for general population, 3 for children, 3 yogurts19 for general population, 3 for children, 3 yogurts
 8 claimed a specific number of organisms per8 claimed a specific number of organisms per servingserving
 13 claimed only a number of organisms13 claimed only a number of organisms at time ofat time of
manufacturemanufacture
 8/25 contained less than 1 percent of the claimed8/25 contained less than 1 percent of the claimed
number of live bacteria or of the expected minimum ofnumber of live bacteria or of the expected minimum of
1 billion.1 billion.
 7 of the 8 that gave expected numbers per serving met7 of the 8 that gave expected numbers per serving met
those countsthose counts
 None contaminatedNone contaminated with bacteria, mold, or funguswith bacteria, mold, or fungus
 All enteric-coated capsules passed testingAll enteric-coated capsules passed testing

75. Probiotics: recommendingProbiotics: recommending
Lactobacillus rhamnosus GG, reuterii,Lactobacillus rhamnosus GG, reuterii, bestbest
studied to datestudied to date
Combination products not well studied, butCombination products not well studied, but
may work as wellmay work as well
Typical effective “dose”: 10 billionTypical effective “dose”: 10 billion
organisms/dorganisms/d
Most require refrigerationMost require refrigeration
Can give in cool food/drinkCan give in cool food/drink

76. ProbioticsProbiotics
Living organisms which upon ingestionLiving organisms which upon ingestion
in sufficient numbers , exert healthin sufficient numbers , exert health
benefits beyond basic nutrition.benefits beyond basic nutrition.
PrebioticsPrebiotics
Nondigestible oligosaccharides foodNondigestible oligosaccharides food
that stimulates the growth of beneficialthat stimulates the growth of beneficial
microorganisms already present in colon.microorganisms already present in colon.
SynbioticSynbiotic
Probiotic & prebiotic mixed together.Probiotic & prebiotic mixed together.

77. Primary Pediatric Uses of ProbioticsPrimary Pediatric Uses of Probiotics
 Manage lactose intolerance (Manage lactose intolerance (L acidophilusL acidophilus))
 Antibiotic-associated diarrhea and infectious diarrheaAntibiotic-associated diarrhea and infectious diarrhea
 DecreaseDecrease constipationconstipation
 Decrease risk ofDecrease risk of NEC and all cause mortality inNEC and all cause mortality in
premature infantspremature infants
 Decrease dental cariesDecrease dental caries
 Treatment ofTreatment of H pyloriiH pylorii infections, UTIinfections, UTI
 Decrease colicDecrease colic
 Decrease risk of developing eczemaDecrease risk of developing eczema
 Decrease upper respiratory tractDecrease upper respiratory tract infectionsinfections