probiotics and prebiotics in pediatrics

DOI: 10.1542/peds.2010-2548; originally published online November 29, 2010; 2010;126;1217Pediatrics

Gastroenterology, Hepatology, and NutritionDan W. Thomas, Frank R. Greer and Committee on Nutrition; Section on

Probiotics and Prebiotics in Pediatrics

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of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1948. PEDIATRICS is owned, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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Clinical Report—Probiotics and Prebiotics inPediatrics

abstractThis clinical report reviews the currently known health benefits ofprobiotic and prebiotic products, including those added to commer-cially available infant formula and other food products for use in chil-dren. Probiotics are supplements or foods that contain viable micro-organisms that cause alterations of the microflora of the host. Use ofprobiotics has been shown to be modestly effective in randomizedclinical trials (RCTs) in (1) treating acute viral gastroenteritis inhealthy children; and (2) preventing antibiotic-associated diarrhea inhealthy children. There is some evidence that probiotics prevent ne-crotizing enterocolitis in very low birth weight infants (birth weightbetween 1000 and 1500 g), but more studies are needed. The results ofRCTs in which probiotics were used to treat childhood Helicobacterpylori gastritis, irritable bowel syndrome, chronic ulcerative colitis,and infantile colic, as well as in preventing childhood atopy, althoughencouraging, are preliminary and require further confirmation. Probi-otics have not been proven to be beneficial in treating or preventinghuman cancers or in treating children with Crohn disease. There arealso safety concerns with the use of probiotics in infants and childrenwho are immunocompromised, chronically debilitated, or seriously illwith indwelling medical devices.

Prebiotics are supplements or foods that contain a nondigestible foodingredient that selectively stimulates the favorable growth and/or ac-tivity of indigenous probiotic bacteria. Human milk contains substan-tial quantities of prebiotics. There is a paucity of RCTs examining pre-biotics in children, although there may be some long-term benefit ofprebiotics for the prevention of atopic eczema and common infectionsin healthy infants. Confirmatory well-designed clinical research stud-ies are necessary. Pediatrics 2010;126:1217–1231

INTRODUCTIONMicrobes are ubiquitous and are important factors in the overallhealth of humans as well as the Earth. Efforts to optimize the intes-tinal microbial milieu have increased the interest in adding probi-otics and prebiotics to nutritional products. As with antibiotics, theuse and efficacy of probiotics and prebiotics should be supportedby evidenced-based medicine. The purpose of this clinical report isto review the medical uses of probiotics and prebiotics and tosummarize what is currently known about their health benefits asdietary supplements added to food products marketed to children,including infant formula. The guidance in this report will help pedi-atric health care providers to make appropriate decisions regard-

Dan W. Thomas, MD, Frank R. Greer, MD, and COMMITTEEON NUTRITION; SECTION ON GASTROENTEROLOGY,HEPATOLOGY, AND NUTRITION

KEY WORDSprobiotics, prebiotics, pediatrics, supplements, nutrition

ABBREVIATIONSLGG—Lactobacillus rhamnosus GGFOS—fructo-oligosaccharideIBD—inflammatory bowel diseaseRCT—randomized controlled trialCI—confidence intervalRR—relative riskOR—odds ratioNEC—necrotizing enterocolitisCUC—chronic ulcerative colitisIBS—irritable bowel syndromeGOS—galacto-oligosaccharideFDA—Food and Drug Administration

The guidance in this report does not indicate an exclusivecourse of treatment or serve as a standard of medical care.Variations, taking into account individual circumstances, may beappropriate.

This document is copyrighted and is property of the AmericanAcademy of Pediatrics and its Board of Directors. All authorshave filed conflict of interest statements with the AmericanAcademy of Pediatrics. Any conflicts have been resolved througha process approved by the Board of Directors. The AmericanAcademy of Pediatrics has neither solicited nor accepted anycommercial involvement in the development of the content ofthis publication.

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All clinical reports from the American Academy of Pediatricsautomatically expire 5 years after publication unless reaffirmed,revised, or retired at or before that time.

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2010 by the American Academy of Pediatrics

FROM THE AMERICAN ACADEMY OF PEDIATRICS

Guidance for the Clinician inRendering Pediatric Care

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ing the usefulness and benefit of pro-biotics and prebiotics for theirpatients.

DEFINITIONS

Probiotic: An oral supplement or afood product that contains a sufficientnumber of viable microorganisms toalter the microflora of the host andhas the potential for beneficial healtheffects.1–3

Prebiotic: A nondigestible food ingre-dient that benefits the host by selec-tively stimulating the favorable growthand/or activity of 1 ormore indigenousprobiotic bacteria.1–4

Synbiotic: A product that containsboth probiotics and prebiotics. Evi-dence for synergy of a specific prebi-otic for a probiotic in the product is notessential. Synbiotics may be separatesupplements or may exist in functionalfoods as food additives.1–3

Postbiotic: A metabolic byproductgenerated by a probiotic microorgan-ism that influences the host’s biologi-cal functions.5,6

Functional food: Any modified food orfood ingredient that provides a healthbenefit beyond that ascribed to anyspecific nutrient/nutrients it contains.It must remain a food, and it must dem-onstrate its effect in amounts normallyexpected to be consumed in the diet.Benefits may include functions rele-vant to improving health and well-being and/or reduction of risk of dis-ease. Any food that contains probioticsor prebiotics is a functional food. Anexample of a functional food is live-culture yogurt that contains probioticbacteria, prebiotics, and other dietarynutrients. Human milk may also beconsidered a functional food; it con-tains substantial amounts of oligosac-charides (prebiotics) and may containsome naturally occurring probioticbacteria (103 of bifidobacteria per mLof expressed human milk, as reportedin 1 study).7

WHAT ARE PROBIOTICS?

Probiotic microorganisms are typi-cally members of the genera Lactoba-cillus, Bifidobacterium, and Strepto-coccus.1–3,8–14 These bacteria arefermentive, obligatory, or facultativeanaerobic organisms, which are typi-cally nonmotile and of varying shapes.They typically produce lactic acid.Their inherent biological features en-able them to predominate and prevailover potential pathogenic microorgan-isms in the human digestive tract. It iscurrently hypothesized that these mi-crobes generate small molecular met-abolic byproducts that exert beneficialregulatory influence on host biologicalfunctions, including short-chain fattyacids such as butyrate. These meta-bolic byproducts are sometimes re-ferred to as “postbiotics” and mayfunction biologically as immune modu-lators.5,6,15 The most studied probioticbacteria to date include Lactobacillusrhamnosus GG (LGG), Bifidobacteriumlactis, and Streptococcus thermophi-lus. These probiotic bacteria arebiologically different from the Gram-negative, motile, non–lactic-acid–producing bacteria such as Klebsiella,Pseudomonas, Serratia, and Proteusspecies, which also may be prominentflora in the human digestive system.These potentially harmful bacteriamay translocate across the intestinalepithelium and could result in diseasein humans.16,17 Some yeasts and yeastbyproducts have also been studied andhave been frequently used as probi-otic agents, such as the yeast Sac-charomyces boulardii. Probiotic bac-teria can be delivered and ingestedseparately as medicinals or supple-ments. They can also be mixed with,added to, or naturally exist in func-tional foods.

WHAT ARE PREBIOTICS?

Prebiotics are usually in the form ofoligosaccharides, which may occur

naturally but can also be added as di-etary supplements to foods, bever-ages, and infant formula.4 Although in-digestible by humans, their presencein the digestive system selectively en-hances proliferation of certain probi-otic bacteria in the colon, especiallyBifidobacteria species. Prebiotic oligo-saccharides often contain fructosechains with a terminal glucose andtypically consist of 10 or fewersugar molecules. Examples of prebi-otic oligosaccharides include fructo-oligosaccharides (FOSs), inulin,galacto-oligosaccharides (GOSs), andsoybean oligosaccharides. Inulin is acomposite oligosaccharide that con-tains several FOS molecules. The com-plex polysaccharides that constitutedietary fiber can also be considered tobe prebiotic agents.

Although dietary nucleotides do not fitthe exact definition of a prebiotic, theyare prebiotic-like agents and have im-munomodulating and direct intestinalbiological properties.18 Some infantformulas contain a limited amount ofadded free nucleotides (7–20mg/dL).18

Human milk, on the other hand, con-tains a substantial but variableamount of oligosaccharides (14 g/L) aswell as free nucleotides (up to 20% ofnonprotein nitrogen).19 Some infant-formula manufacturers now addprebiotic oligosaccharides to theirproducts.

Beverages and nutritional supple-ments marketed for older infants, chil-dren, and adults contain oligosaccha-rides and nucleotide additives invarying amounts.

INTESTINAL BACTERIALCOLONIZATION AND DEVELOPMENTOF THE INTESTINAL MUCOSALDEFENSE SYSTEM

Similar to the fetus, an infant at thetime of birth has a sterile gastrointes-tinal tract, but bacterial colonizationoccurs rapidly.20–22 The newborn in-

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fant’s gestational age, mode of deliv-ery, and diet seem to have significanteffects on this process. Neonates whoare born by Caesarian delivery, bornpreterm, and/or exposed to perinatalor postnatal antibiotics have a delay inintestinal commensal probiotic bacte-rial colonization. When delivered vagi-nally, breastfed infants and formula-fed infants have a similar pattern ofbacterial colonization at 48 hours ofage. However, by 7 days of age, approx-imately two-thirds of formula-fed in-fants have a predominance of Bacte-roides fragilis, compared with only22% of breastfed infants.20

Toward the end of the first month oflife in developing countries, breast-fed infants are found to haveBifidobacteria-predominant coloniza-tion, whereas formula-fed infantshave equal colonization with Bacte-roides and Bifidobacteria species. Inresource-rich countries, however, dif-ferences are less pronounced be-tween breastfed and formula-fedinfants.15

The composition of intestinal micro-flora does not change significantly af-ter infancy. Therefore, the compositionof fecal flora in older children andadults is less variable and not as de-pendent on diet. In fact, beyond in-fancy, bacterial concentrations in thecolon are typically 1012 colony-formingunits per mL of intestinal contents (10-fold the total number of human cells inthe human body), and anaerobic bac-teria far outnumber aerobic coli-forms.23 Typically, 500 different bacte-rial species contribute to an adult’scolonic microflora, but 99% of the mi-croflora are accounted for by 30 to 40species.23 The descriptive terms of“microbiota” and “microbiome” arenewer terms that are replacing suchterms as “microflora” in an attempt byresearchers in the field to better de-fine one’s microbial environment.24

“Microbiota” refers to a population of

microscopic organisms that inhabit abodily organ or portion of a person’sbody, and human “microbiome” refersto the unique entire population of mi-croorganisms and their complete ge-netic elements that inhabit one’sbody.

The intestinal mucosal defense systemis an integral part of a sophisticatedimmunoregulatory network that in-cludes the intestinal microflora.21,25–30

Recognition of self- and non–self-antigens begins early in life, perhapseven in utero, and is significantly influ-enced by events that occur within thedigestive system soon after birth. Theimmunoresponsiveness of the diges-tive system is significantly affected bythe young infant’s diet, state of bacte-rial colonization, and early exposure topotential infectious pathogens and an-tibiotics as well as the infant’s geno-type. It is thought that the occurrenceof many diseases, both intestinal andnonintestinal, can be related to dys-regulation or interference with theearly development of the intestinalmu-cosal defense system.28,29 Examples ofthese diseases include those thoughtto be atopic (asthma, eczema, and al-lergic rhinitis) or autoimmune (multi-ple sclerosis, type 1 diabetes mellitus,and chronic inflammatory bowel dis-ease [IBD]).28 Certainly, the overridingdetermining factor in development ofthe immune system is one’s geneticpredisposition.25

The molecular basis for innate and ac-quired immunity is thought to reside inthe recognition and response of ma-ture T lymphocytes to trigger mole-cules, such as those derived fromdietary and bacterial-breakdown prod-ucts within the intestinal tract.29 Trig-ger molecules also include dietary nu-cleotides and oligosaccharides. Toll-like receptors located in the surfacemembrane of T lymphocytes facilitaterecognition of these triggermolecules,which eventually leads to specialized

T-lymphocyte recognition and re-sponse to subsequent exposure to thesame or very similar molecules. Thus,T-lymphocyte recognition of specificoligosaccharides bound to intestinalpathogens plays an important role inpreventing gastrointestinal illness.

Given these important influences on in-testinal microflora colonization and im-mune function, the infant’s early diet andintestinal microbial environment arethought to serve as pivotal factors inoverall health. Probiotic bacteria, postbi-otic bacterial byproducts, and dietaryprebiotics are believed to exert positiveeffects on the development of the muco-sal immune system. It is also believedthat exposure to “nonbeneficial” micro-organisms and antimicrobial agents inthe newborn period may result in im-mune dysregulation in susceptible indi-viduals and may lead to some chronicdisease states. There is evidence that hu-man milk contains mononuclear cellsthat traffic intestinally derived bacterialcomponents from the mother to her in-fant. The ingested human milk contain-ing the bacterial components derivedfrom the mother are thought to influ-ence her young infant’s developing im-mune system. This process is termed“bacterial imprinting,” and its overallbiological effect requires furtherstudy.31

USE OF PROBIOTICS INPREVENTION AND TREATMENT OFCLINICAL DISEASES

Reviews on the clinical applications ofprobiotics and prebiotics can be foundin the references.4,8–14 Results ofevidence-based analyses of the clinicaleffectiveness of probiotics and prebi-otics are discussed below. It must bestressed that the current lack of evi-dence of efficacy does not mean thatfuture clinical research will not estab-lish significant health benefits for pro-biotics and prebiotics.






Acute Infectious Diarrhea

Prevention of Acute InfectiousDiarrhea

Results of published randomized con-trolled trials (RCTs) have indicatedthat there is modest benefit of givingprobiotics in preventing acute gastro-intestinal tract infections in healthy in-fants and children.32–35 Most of thestudies were conducted in child carecenters. The strains of probiotics usedincluded LGG, S thermophilus, Lactoba-cillus casei, B lactis, or Lactobacillusreuteri mixed with milk or infant for-mula or given as an oral supplement.Rotavirus was the most commoncause of acute diarrhea in the RCTs.

In a double-blind, placebo-controlledtrial by Weizman et al,36 201 infants(4–10months of age) received either aprobiotic-supplemented formula con-taining either B lactis or L reuteri or acontrol formula without an added pro-biotic over a 12-week study period. Thestudy was conducted at 14 differentchild care centers over a 2-yearperiod. Infants fed a probiotic-supplemented formula had fewer andshorter episodes of diarrhea than didinfants in the control group. Infants inthe control group had a mean of 0.59days of diarrhea (95% confidence in-terval [CI]: 0.34–0.84 days) per infantcompared with 0.37 days (95% CI:0.08–0.66 days) in the B lactis and 0.15days (95% CI: 0.12–0.18 days) in the Lreuteri probiotic-supplemented studygroups (P� .001). During the 12-weekstudy period, the infants in the controlgroup were found to have a mean of0.31 episodes of diarrhea (95% CI:0.22–0.44 episodes) compared with0.12 episodes (95% CI: 0.05–0.21 epi-sodes) and 0.02 episodes (95% CI:0.01–0.05 episodes) in the B lactis–and L reuteri–supplemented studygroups, respectively (P� .001). Therewas no significant effect found on theincidence of acute respiratory ill-nesses. In another study conducted in

child care centers in France,37 928healthy children were randomly as-signed to be fed either standard yogurtor yogurt supplemented with L caseifor 4 months. The children who werefed the probiotic-supplemented yogurthad fewer episodes of diarrhea duringthe study period than did those whowere fed standard yogurt (15.9% vs22%; P� .03).

The results of a meta-analysis of probi-otic prevention of acute rotavirus gas-troenteritis in child care centers indi-cated that approximately 7 childrenwould need to have been given LGG toprevent 1 child from developing noso-comial rotavirus gastroenteritis in achild care center setting.38 To date, theavailable data do not support routineuse of probiotics to prevent nosoco-mial rotavirus diarrhea in child carecenters. However, there may be spe-cial circumstances in which probioticuse in children in long-term healthcare facilities or in child care cen-ters is beneficial. The use of thenewly available pentavalent rotavi-rus vaccine in the United States39 willlikely be a more formidable preven-tative agent than the use of probiot-ics in reducing the incidence of themost common form of acute infantileinfectious diarrhea.

Treatment of Acute InfectiousDiarrhea

Well-conducted RCTs in healthy chil-dren in developed countries have pro-vided good data on the therapeuticbenefit of probiotics in children withacute infectious diarrhea. In a random-ized, double-blind, placebo-controlledtrial by Szymanski et al,40 administra-tion of LGG significantly shortened theduration of acute rotavirus diarrheaby a mean of 40 hours, but duration ofdiarrhea of any other etiology was notaffected. Probiotic administration alsoshortened the time necessary for in-travenous rehydration by a mean of 18

hours. Results of several other meta-analyses41–43 and a Cochrane review44

have been published on the benefit ofprobiotics for treatment of acute infec-tious diarrhea in children. These re-ports indicate that probiotics reducethe number of diarrheal stools and theduration of the diarrhea by approxi-mately 1 day. The benefit is strain-dependent. LGG is the most effectiveprobiotic reported to date and is dose-dependent for doses greater than 1010

colony-forming units. Probiotics alsoseem to be more effective when givenearly in the course of diarrhea and aremost helpful for otherwise healthy in-fants and young children with waterydiarrhea secondary to viral gastroen-teritis but not invasive bacterial infec-tions. Thus, there is evidence to sup-port the use of probiotics, specificallyLGG, early in the course of acute infec-tious diarrhea to reduce the durationby 1 day.

Antibiotic-Associated Diarrhea

Prevention of Antibiotic-AssociatedDiarrhea

Meta-analysis of published resultsof RCTs of probiotic use in the pre-vention of antibiotic-associated di-arrhea in children indicates a benefi-cial effect.45–48 Treatment with aprobiotic was started when antibiotictherapy was initiated for treatment ofan acute respiratory infection (otitismedia) in most of these studies. Treat-ment with probiotics compared withplacebo reduced the risk of developingantibiotic-associated diarrhea from28.5% to 11.9% (relative risk [RR]: 0.44[95% CI: 0.25–77]; P � .006).45 LGG, Blactis, S thermophilus, and S boulardiihave been the most common agentsused in RCTs. Approximately 1 in 7cases of antibiotic-associated diar-rhea was prevented by the use of aprobiotic.45 Children in these stud-ies received either a probiotic-supplemented formula or a separate




probiotic as preventive treatment. Ac-cording to 1 reported meta-analysis,probiotic treatment significantly re-duced odds of antibiotic-associated di-arrhea as compared with placebo(odds ratio [OR]: 0.39 [95% CI: 0.25–0.62]; P � .001) for both the yeast by-product S boulardii and LGG. Therewas no significant difference betweenthe 2 treatments; the overall combinedOR was 0.37 (95% CI: 0.26–0.53; P �.001) in favor of active probiotic treat-ment over placebo.48 Thus, probioticscan be used to reduce the incidence ofantibiotic-associated diarrhea.

Treatment of Antibiotic-AssociatedDiarrhea

There have been no published RCTs ofchildren that have investigated the ef-fect of probiotics for treatment ofantibiotic-associated diarrhea. Thus,their use cannot be recommended. Theclinician who is caring for a childwith antibiotic-induced diarrheamust weigh the benefits of consider-ing therapy with a probiotic or dis-continuing or modifying the antibi-otic treatment when possible. NoRCTs have been published concern-ing treatment with probiotics ofchildren with Clostridium difficileantibiotic-associated diarrhea.

Atopic Diseases

Prevention of Atopic Disease

As previouslymentioned, the sequenceof bacterial intestinal colonization ofneonates and young infants is proba-bly important in the development ofthe immune response.21 Recognitionby the immune system of self and non-self, as well as the type of inflamma-tory responses generated later in life,are likely affected by the infant’s dietand acquisition of the commensal in-testinal bacterial population superim-posed on genetic predisposition.During pregnancy, the cytokineinflammatory-response profile of the

fetus is diverted away from cell-mediated immunity (T-helper 1 [Th1]type) toward humoral immunity (Th2type). Hence, the Th2 type typically isthe general immune response in earlyinfancy. The risk of allergic diseasecould well be the result of a lack ordelay in the eventual shift of the pre-dominant Th2 type of response tomoreof a balance between Th1- and Th2-typeresponses.49 Administration of probi-otic bacteria during a time period inwhich a natural population of lactic-acid–producing indigenous intestinalbacteria is developing could theoreti-cally influence immune developmenttoward more balance of Th1 and Th2inflammatory responses.50 The intesti-nal bacterial flora of atopic childrenhas been demonstrated to differ fromthat of nonatopic children. Specifically,atopic children have more Clostridiumorganisms and fewer Bifidobacteriumorganisms than do nonatopic studysubjects,15,51 which has served as therationale for the administration of pro-biotics to infants at risk of atopic dis-eases, particularly for those who areformula fed.

In a double-blinded RCT, LGG or a pla-cebo was given initially to 159 womenduring the final 4 weeks of pregnancy.If the infant was at high risk of atopicdisease (atopic eczema, allergic rhini-tis, or asthma), the treatment was con-tinued for 6 months after birth in boththe lactating woman and her infant.52 Atotal of 132 mother-infant pairs wererandomly assigned to receive eitherplacebo or LGG and treated for 6months while breastfeeding. The pri-mary study end point was chronic re-current atopic eczema in the infant.Atopic eczema was diagnosed in 46 of132 (35%) of these study children by 2years of age. The frequency of atopiceczema in the LGG-treated group was15 of 64 (23%) versus 31 of 68 (46%) inthe placebo group (RR: 0.51 [95% CI:0.32–0.84]; P � .01). The number of

mother-infant pairs required to betreated with LGG to prevent 1 case ofchronic recurrent atopic eczema was4.5. By 4 years of age, eczema occurredin 26% of the infants in the grouptreated with LGG, compared with 46%in the placebo group (RR: 0.57 [95% CI:0.33–0.97]; P � .01). However, only67% of the original study group wasanalyzed at the 4-year follow-up. Theseresults support a preventive effect forgiving a probiotic to mothers late inpregnancy and to bothmothers and in-fants during the first 6 months of lac-tation for the prevention of atopic ec-zema in infants who are at risk ofatopic disease. However, these resultshave not been confirmed in subse-quent clinical trials, as summarized ina recent review by Kopp and Salfeld.53

Conversely, Taylor et al54 found thatprobiotic supplementation did not re-duce the risk of atopic dermatitis inchildren at high risk with the report ofsome increased risk of subsequent al-lergen sensitization. As concluded in areview by Prescott and Björkstén55 andin a 2007 Cochrane review,56 despitethe encouraging results of some stud-ies, there is insufficient evidence towarrant the routine supplementationof probiotics to either pregnantwomen or infants to prevent allergicdiseases in childhood. Explanations forvaried study results include host fac-tors such as genetic susceptibility, en-vironmental factors such as geo-graphic region and diet, and studyvariables including probiotic strainsand doses used.55,57

Treatment of Atopic Disease

In an RCT, 53 Australian infants withmoderate-to-severe atopic dermatitiswere given either Lactobacillus fer-mentum or placebo for 8 weeks. At fi-nal assessment at 16 weeks, signifi-cantly more children who received theprobiotic had improved extent and se-verity of atopic dermatitis as mea-sured by the Severity of Scoring of






Atopic Dermatitis (SCORAD) index overtime compared with those who re-ceived placebo (P� .01).58,59 These re-sults are encouraging, but as summa-rized in a 2008 Cochrane review,60

probiotics have not yet been provento be effective in the treatment ofeczema.

Prevention of NecrotizingEnterocolitis in Low Birth WeightNeonates

A newborn’s gut is sterile at birth,with bacterial colonization beginningshortly after birth.20–22 Preterm infantsfrequently have delayed and aberrantacquisition of the “normal” digestivemicroflora, possibly because of re-stricted enteral feedings and frequentuse of antibiotic therapy.61,62 Delayedenteral feeding, frequent use of antibi-otic therapy, and altered acquisition ofnormal digestive microflora are be-lieved to be primary contributing fac-tors for the increased risk of necrotiz-ing enterocolitis (NEC) in preterminfants63,64 and is the rationale for pro-biotic supplements.

In a 2008 Cochrane review65 based on 9RCTs,66–74 enteral probiotic supplemen-tation significantly reduced both theincidence of NEC (stage II or more) (RR:0.32 [95% CI: 0.17–0.60]) and mortality(RR: 0.43 [95% CI: 0.25–0.75]).65 Noso-comial sepsis was not reduced signifi-cantly (RR: 0.93 [95% CI: 0.73–1.19]). Atotal of 1425 infants who were born atless than 37 weeks’ gestational ageand/or less than 2500 g birth weightwere included in thismeta-analysis. Nosystemic infections or serious adverseevents that were directly attributed tothe administered probiotic organismwere reported for these RCTs. The au-thors concluded that the results oftheir analysis supported a change inclinical practice to supplement pre-term infants who weighed more than1000 g at birth with a probiotic. Dataregarding the outcome of preterm ex-

tremely low birth weight infants whoweighed less than 1000 g at birth couldnot be used by the authors to reliablyestimate the efficacy and safety of pro-biotic supplementation to this high-risk group. A large RCT was recom-mended to investigate the potentialbenefit and safety of probiotic supple-mentation to extremely low birthweight infants.

However, because the of large hetero-geneity of the studies included in theCochrane review,65 caution is urged ininterpreting the results, which aresomewhat problematic. The studies allused different probiotics, includingLGG, Bifidobacterium breve, Saccharo-myces species, and mixtures ofBacteroides bifidus, S thermophilus,Lactobacillus acidophilus, and Bi-fidobacterium infantis. Doses of indi-vidual probiotics varied and were ad-ministered with human milk feedings,formula feedings, or both human milkand formula feedings in some studies.Not all of the studies had the same endpoints, including the primary outcomeof NEC. A second and larger study byLin et al,75 the results of which werepublished after the Cochrane review,repeated the 2005 study71 by using adifferent mixture of probiotics: L aci-dophilus and B bifidus. The overall in-cidence of NEC and death was less inthe second study75 compared with thatin the first71 in the controls, and thesecond study revealed that probioticsdid not reduce the incidence of sepsiscomparedwith that in the first, and theintervention group actually had ahigher incidence of sepsis. The num-ber needed to treat to prevent 1 case ofNEC was 27 in the first study by Lin etal71 and 21 in the second study.75 An-other point that makes the data prob-lematic is that the combinations ofprobiotics used in the Lin et al studies,which are the most convincing for NECprevention, are not available in theUnited States. Not all probiotics have

been studied; therefore, all probioticscannot be generally recommended.

Treatment of Helicobacter pyloriInfection

There is a modest and encouragingbenefit in published RCT results forprobiotics used as adjunctive therapyfor H pylori gastritis in adults.76 OneRCT in children has been published,77

and the results demonstrated that theprobiotics-supplemented treatmentgroup had better H pylori eradicationthan did the placebo group (84.6% vs57.5%; RR: 1.47 [95% CI: 1.1–2.0]). Theadverse effects of diarrhea, nausea,and vomiting in both the placebo andprobiotic treatment group did not dif-fer significantly. Thus, probiotics maybe of some benefit in the eradication ofH pylori in children, but more studiesare required.

Chronic IBD

The term IBD is inclusive of patientswith either chronic ulcerative colitis(CUC) or Crohn disease. It is estimatedthat approximately 40% to 70% of chil-dren and adult patients suffering withIBD routinely use alternative medi-cines, including probiotics, as adjunc-tive or replacement therapy for pre-scribed medications.78–80 In theory,probiotics may be beneficial in thetreatment of IBD.21 It has been pro-posed that in individuals with geneticsusceptibility to IBD, chronic inflam-mation occurs in response to com-mensal digestive microflora becauseof various inherited defects of innateinflammatory-response pathways. Onesuch identified inherited defect foundin patients with Crohn disease is a mu-tation of the CARD15 gene on chromo-some 16, which results in abnormalchronic inflammation in response tobacteria such as Escherichia coli in thedigestive tract.21 Hence, modulatingthe commensal intestinal bacterial en-vironment with probiotic supplements




may reduce the inflammatory re-sponse in patients with IBD.80

Treatment of Chronic UlcerativeColitis

Data from RCTs of probiotics for thetreatment of adults with CUC are en-couraging.81–84 The administration ofprobiotics to adults with mild-to-moderate CUC disease activity hascomparable efficacy when comparedwith treatment with anti-inflammatorydrugs used to treat CUC, such as me-salamine, as reported in a recentlypublished Cochrane review.85 Thesame is true in adult patients with ileo-anal pouchitis after colectomy surgeryfor CUC. Most of these studies use theprobiotic mixture VSL#3 (Sigma-TauPharmaceuticals, Gaithersburg, MD),which is a combination of S thermophi-lus, Bifidobacterium species, and Lac-tobacillus species. The probiotic E coliNissle 1917 (Ardeypharm GmbH, Her-dacke, Germany) has also been usedsuccessfully to treat mild-to-moderatepouchitis or CUC in adults.86 One RCT inwhich 29 children with newly diag-nosed CUC were randomly assigned toreceive either VSL#3 or a placebo for 1year had promising results.87 All studypatients were also given standard cor-ticosteroid induction therapy com-bined with mesalamine maintenancetherapy. Remission occurred in 13 pa-tients (92.8%) in the VSL#3 group and 4patients (36.4%) in the placebo group(P� .001). Relapse occurred in 3 of 13(23%) patients in the VSL#3 group ver-sus 11 of 15 (73.3%) in the placebogroup within the 1-year study period(RR: 0.32 [95% CI: 0.25–0.773]; P �.014). Although these results are prom-ising, more studies are needed inlarger numbers of children to substan-tiate the benefit of probiotics in man-aging children with mild-to-moderateCUC. Thus, probiotics for CUC cannotbe generally recommended at thistime without further confirmatoryresearch.

Treatment of Crohn Disease

One RCT in which LGG was used in pe-diatric patients with Crohn disease re-sulted in no significant benefit.88 Treat-ing adults with Crohn disease with theprobiotics S boulardii, LGG, and E coliNissle 1917 has not yielded promisingresults thus far.89–92 A recent Cochranereview indicated that there is, as yet,no proven benefit for maintaining re-mission by administering probiotics toadults with Crohn disease.93 Becauseof the lack of efficacy, treatment ofCrohn disease with probiotics cannotbe recommended for children.

Irritable Bowel Syndrome andConstipation: Treatment

There has been a single published RCTof the treatment of irritable bowel syn-drome (IBS) in children.94 LGG reducedabdominal distension and discomfortin a group of 50 pediatric patients overa 6-week study period. Response totherapywas recorded and collected ona weekly basis by using the DigestiveSymptom Rating Scale. Various probi-otics were shown to be helpful in sev-eral other RCTs of treatment of IBS inadults.95–97 One published RCT ad-dressed the use of probiotics (LGG) ora placebo as adjunct therapy to a stoolsoftener (lactulose) to treat functionalconstipation in 84 children.98 LGG wasnot an effective adjunct to lactulose intreating constipation in children. Thus,probioticsmay be of benefit in childrenwith IBS on the basis of a single RCT,but a recommendation for them usecannot bemadewithout further confir-matory studies. Probiotics cannot berecommended at this time for treat-ment of constipation.

Infantile Colic

Prevention of Colic

To date, no RCTs have been conductedwith colic as a primary end point.

Treatment of Colic

Colic is a common condition that typi-cally affects infants in the first 4months of life. The primary mecha-nism remains unknown. Available evi-dence suggests that colic potentiallyhas a number of independent causes,including dietary protein hypersensi-tivity.99,100 A recent unblinded RCT ex-amined the effect of the administra-tion of L reuteri versus simethicone inthe treatment of colic in 90 exclusivelybreastfed infants in Italy.100 The admin-istration of L reuteri improved thesymptoms of colic (minutes of cryingper day) within 1 week of treatment,compared with simethicone therapy.The breastfeeding mothers were in-structed to eliminate dairy productsfrom their diets during the study pe-riod to minimize potentially confound-ing adverse effects of dietary proteinhypersensitivity. The authors of thestudy proposed several theories for apositive therapeutic benefit, includingprobiotic modulation of proinflamma-tory responses. Further confirmatoryRCTs are required to recommend rou-tine use of probiotics in the treatmentof infantile colic in both breastfed andformula-fed infants. On the basis oflimited information, probiotics may beof benefit in treatment of colic in exclu-sively breastfed infants, but morestudies are needed before they can berecommended.

Extraintestinal Infections

Prevention of ExtraintestinalInfections

In a 2001 RCT in 17 Finnish child carecenters, 571 healthy children 1 to 6years of age were studied for 7monthsin winter.33 Children were randomlyassigned to receive milk 3 times perday with or without LGG. When the datawere adjusted for age, children whowere fed milk with LGG, compared withcontrols, did not have significantlyfewer days with respiratory symptoms






or fewer days of child care absencesbecause of illness. There were also nosignificant differences in the numbersof children with a doctor’s diagnosis ofinfection or number of prescriptionsfor antibiotics when adjusted for age,although the trends favored the chil-dren who were fedmilk with LGG. Thus,probiotics for the prevention of ex-traintestinal infections in children can-not be recommended at this time.

Treatment of ExtraintestinalInfections

No RCTs in children have demon-strated definite beneficial effects ofadministering probiotics to treat ex-traintestinal infections. The beneficialeffects that have been reported in un-controlled trials in adults with 1 ormore types of extraintestinal infectionhave typically used LGG as a supple-ment or probiotics added to dairyproducts.101–103 Thus, probiotics arenot recommended for children fortreatment of extraintestinal infections.

Cancer: Prevention and Treatment

Results of published studies have dem-onstrated the positive benefits of func-tional foods, such as yogurt, and the ad-ministration of probiotics to preventcarcinogenic processes in animal mod-els.104 As yet, no published RCTs warrantrecommendation of routine administra-tion of probiotics to either treat or pre-vent cancer in adults or children.

USE OF PREBIOTICS INPREVENTION AND TREATMENT OFCLINICAL DISEASES

Few RCTs have been conducted to eval-uate the use of prebiotics in prevent-ing or treating specific childhooddiseases.8

Prevention and Treatment ofAllergy

A 2007 Cochrane review105 concludedthat there was inconclusive evidencefor giving prebiotics to prevent allergic

disorders in infants. However, in 2008,Arslanoglu et al106 reported on a 2-yearfollow-up of an RCT in 132 infants atrisk of atopy because of parentalatopy. Infants were fed a partially hy-drolyzed formula with either an addedmixture of FOS and GOS or maltodex-trin placebo in the first 6months of life.Those given the prebiotic mixture ofFOS and GOS had a reduced incidenceof atopic disease. Cumulative inci-dences of atopic eczema, recurrentwheezing, and allergic urticaria werehigher in the maltodextrin placebogroup (27.9%, 20.6%, and 10.3%, re-spectively) than in the interventiongroup (13.6%, 7.6%, and 1.5%) (P �.05). In a 2009 review, van der Aa et al107

analyzed relevant publications to dateand concluded that there is presentlynot enough evidence to support theuse of probiotics, prebiotics, or synbi-otics for the prevention or treatmentof allergic dermatitis in children. Con-firmatory studies of the benefits ofprebiotics, especially for children fedformula that is not partially hydrolyzedor infants fed partially hydrolyzed for-mula, which are already being promotedto reduce the incidence of atopic dis-ease, are needed before any recommen-dations can be made for the use of pre-biotics in infants and toddlers to preventinfection or atopic disease.

Other Disorders

It has been shown that the addition ofdietary fiber has ameliorated diar-rheal stools when added to infant for-mula.108 Prebiotics, such as oligosac-charides, inulin, and dietary fibersupplements that are contained inbran, psyllium, and barley fiber, arebeneficial in maintaining clinical re-mission in adult patients with CUC,109

but no RCT results support their use.There have been controlled animal re-search studies that have shown thatprebiotics may prevent or lessen car-cinogenic processes,104 but there havebeen no RCTs in humans.

COMBINED PREBIOTICS ANDPROBIOTICS TO PREVENT ALLERGY

Clinical benefit in preventing allergicdiseases by co-therapy with probioticsand prebiotics in pregnant women andtheir infants was demonstrated in anRCT in Finland.110 A total of 1223 preg-nant women who had been identifiedto deliver infants who would be at highrisk of atopic disease because of pa-rental atopic disease history were ran-domly assigned to be given a mixtureof 4 probiotic strains plus GOS or pla-cebo daily for 2 to 4 weeks before de-livery. After delivery, their infants theneither received the same probioticmixture plus GOS or the same placeboas the mother. Probiotic/prebiotictreatment showed no effect on the cu-mulative occurrence of allergic dis-eases but tended to reduce im-munoglobulin E–associated (atopic)diseases (OR: 0.71 [95% CI: 0.50–1.00];P � .052). Probiotic and prebiotictreatment reduced the occurrence ofeczema (OR: 0.74 [95% CI: 0.55–0.98];P� .035) and atopic eczema (OR: 0.66[95% CI: 0.46–0.95]; P � .025). Confir-matory studies are necessary.

PREBIOTICS AND PROBIOTICS ININFANT FORMULA

Prebiotics

Asmentioned earlier in this review, hu-man milk contains a number of sub-stances that are prebiotic, the mostplentiful of which are oligosaccha-rides.19,30 Oligosaccharide prebioticsare also added to many commerciallyavailable dietary food supplements.Regarding their addition to infant for-mula, the European Commission’s Sci-entific Committee on Food concludedin 2003111 that they had no major con-cerns regarding the addition ofoligosaccharides to infant formulas,including follow-up infant formulas(formulas modified especially for 6- to12-month-old infants), up to a total




concentration of 0.8 g/dL in ready-to-feed formula products.

Few RCTs have examined the effects ofadding prebiotic oligosaccharides toinfant formula.106,112,113 Boehm et al113

studied the effect of the addition of oli-gosaccharides at a concentration of 1g/dL to preterm infant formula for 1month (90% GOSs and 10% FOSs).Stool bifidobacteria counts in theoligosaccharide-supplemented groupincreased significantly comparedwith the nonsupplemented group, andthe bifidobacteria counts reachedthe range of a breastfed referencegroup. In a separate study, Moro etal114 fed term infants the sameoligosaccharide-supplemented for-mula. These infants had higher countsof bifidobacteria as well as lactobacilliin their stools. Schmelzle et al115 con-ducted a multicenter trial that also ex-amined the efficacy of the addition ofprebiotics to infant formula. They re-ported good overall tolerance and noadverse effects during the 12-weekstudy period. A large multicentertrial to evaluate the safety of FOS-supplemented infant formula was con-ducted in the United States in 2004.116

The study demonstrated that infantgrowth was maintained during the 12-week study period for the FOS-supplemented infant-formula groupwithout any adverse effects. Afterweaning infants from formula, the ad-dition of prebiotics to solid food seemsto have a bifidogenic effect, as shownby the results of a recently publishedRCT by Scholtens et al.117 Infant formu-las that contain either GOS or FOS arenow marketed in the United States.However, more information, includingdata from RCTs, is needed before theefficacy of adding prebiotics to infantformulas can be determined.

Probiotics

Two infant formulas currently containa probiotic. One contains B lactis, and

the other contains LGG. These probiot-ics are only added to powdered formu-las at present. The rationale for addingprobiotic organisms to infant formulawas discussed in the introduction ofthis clinical report. The overall health-benefit efficacy of adding probiotics toinfant formula remains to be demon-strated in large RCTs.

SAFETY OF PROBIOTICS ANDPREBIOTICS IN INFANTS ANDCHILDREN

Concerns exist about the overall safetyof administering probiotic products tohigh-risk patient groups, includingadults, children, and term and pre-term infants. Cases of serious infec-tion have occurred and been reportedin the literature.10,118–125 Patients at riskwould be those who are immunocom-promised, including ill preterm neo-nates, and/or children who have intra-venous catheters or other indwellingmedical devices. In most cases, the of-fending organism that caused the sep-sis seems to have stemmed frombacteria from the individual’s own en-dogenous flora. Sepsis has also beenreported in adults, children, and in-fants who received probiotic supple-ments.118,124–126 Land et al126 recently re-ported LGG probiotic sepsis occurringin immunocompromised infants andchildren. A medically fragile infant 6weeks of age became septic with astrain of LGG that was being providedas a supplement. Molecular DNA-fingerprinting confirmed that the LGGprobiotic supplement was the bacte-rial isolate from the infant. Neonatalsepsis and meningitis that were ap-parently associated with the adminis-tration of a probiotic supplement werealso reported.118,120

A recent report focused on probiotictolerance and safety in healthy terminfants who were randomly assignedto be given a high-dose probiotic for-mula, a low-dose probiotic formula, or

control formula for 18 months.35 Therewere no apparent reported adverseevents. All infants demonstrated nor-mal growth. Reports of colic weresignificantly fewer in the 2 probiotic-formula–fed groups, and the fre-quency of health care visits and antibi-otic use was less (P� .001) comparedwith those in the control formulagroup. In a separate study, Petschowet al127 reported that healthy term in-fants given varying amounts of LGG ininfant formula for 2 weeks resulted ingood overall feeding tolerance withsuccessful intestinal tract coloniza-tion, without adverse events.

The apparent safety to date of addingprebiotics to infant formula has beenevaluated in the previously discussedRCTs reported by Boehm et al,113 Moroet al,114 Schmelzle et al,115 and Bettlerand Euler.116

SUMMARY ON SAFETY

The Committee on Nutrition of the Eu-ropean Society of Pediatric Gastroen-terology, Hepatology and Nutrition pre-viously concluded that more studiesare required to establish the safetyand efficacy of probiotic and prebioticproducts in children.12 To date, theseproducts seem to be safe for healthyinfants and children. The committeealso stated that it would be optimal tohave a centralized mechanism of over-sight to ensure probiotic microorgan-ism safety, identity, and geneticstability.12 Centralized oversight andprobiotic product monitoring was alsorecommended in a report from theFood and Agriculture Organization ofthe United Nations World Health Orga-nization.1,2,128 This organization sup-ports the addition of prebiotic prod-ucts to infant formulas designed asfollow-up formulas meant for infantsaged 5 months and older. It was rea-soned that these infants are morelikely to have a more mature immuneresponse and established intestinal






colonization. In terms of oversight andproduct safety in the United States,products marketed as dietary supple-ments, such as probiotics, do not re-quire premarket review and approvalby the US Food and Drug Administra-tion (FDA). However, probiotics or pre-biotics that are marketed specificallyfor the treatment or prevention of adisease are classified as biologicalproducts and do require FDA reviewand approval. Infant formulas must bemade with compliance with what areconsidered good manufacturing prac-tices under the Infant Formula Act of1980 and are under the regulatory aus-pices of the FDA129 because these prod-ucts are often used as the sole sourceof nutrition by infants during a criticalperiod of growth and development.Additional statutory and regulatoryrequirements address appropriate in-fant formula manufacture, composi-tion, and nutrient content. All ingredi-ents used in infant formula must besafe and lawful—that is, food ingredi-ents that are, to date, generally re-garded as safe (GRAS) for use in infantformula and those that are used in ac-cordance with the food-additive regu-lations of the FDA. Prebiotics andprobiotics now being added to com-mercial infant formulas are classifiedas GRAS. Information on FDA regula-tions for infant formula and food ingre-dients and packaging may be found atwww.fda.gov/Food/FoodSafety/Product-SpecificInformation/InfantFormula/default.htm and www.fda.gov/Food/FoodIngredientsPackaging/default.htm.

DEVELOPMENT OF THIS REPORT

The AAP Committee on Nutrition andSection on Gastroenterology, Hepatol-ogy, and Nutrition used review of theliterature, including Cochrane re-views, and reports from othergroups.12,111,128 Comments also weresolicited from committees, sections,and councils of the AAP; 9 entitiesresponded.

Additional comments were soughtfrom the Centers for Disease Controland Prevention, the National Institutesof Health, the US Department of Agri-culture, and the FDA because thesegovernmental agencies have official li-aisons to the Committee on Nutritionand were present during the develop-ment of the statement. For recommen-dations for which high levels of evi-dence are absent, the expert opinionsand suggestions of themembers of theCommittee on Nutrition and othergroups and authorities consultedwere taken into consideration in devel-oping this clinical report.

SUMMARY

1. Humanmilk, a natural prebiotic, ispreferred for infants through 6months of age.130 The oligosaccha-ride content of human milk is sub-stantial and is part of the prebioticcomponents of the human milk.Breastfed infants typically have apreponderance of naturally occur-ring probiotic bacteria in their di-gestive systems. There may besome naturally occurring probi-otic bacteria contained in humanmilk.

2. There is some evidence in other-wise healthy infants and youngchildren to support the use of pro-biotics early in the course of diar-rhea from acute viral gastroenter-itis and that use of probioticsreduces its duration by 1 day.However, the available evidencedoes not support the routine useof probiotics to prevent infectiousdiarrhea unless there are specialcircumstances. There is someevidence to support the use of pro-biotics to prevent antibiotic-associated diarrhea but no evi-dence that it is beneficial fortreatment.

3. Although the results of some stud-ies support the prophylactic use

of probiotics during pregnancyand lactation and during the first 6months of life in infants who are atrisk of atopic disorders, furtherconfirmatory evidence is neces-sary before a recommendation forroutine use can be made.

4. There is some evidence to supportthe use of probiotics to preventNEC in preterm infants with a birthweight of 1000 g or higher. How-ever, the amount and specificity ofwhich probiotic or mixture of pro-biotics to use is problematic, giventhe many unanswered questionsfrom a review of the available lit-erature. Furthermore, many of theprobiotics used and cited in the lit-erature for treatment in preterminfants are not readily available.

5. At the present time, the sustainedor long-term benefit of using pro-biotics for treating disorders suchas Crohn disease, IBS, constipa-tion, and extraintestinal infectionsrequires further RCTs and cannotbe recommended in children. Theremay benefit for treating H pylori in-fections,CUC,and infantile colicwithprobiotics in childhood, but furtherstudies are necessary.

6. Long-term health benefits of pro-biotics in the prevention of cancer,allergy, or other diseases or pro-viding sustained beneficial resultson the developing immune systembeyond early infancy remain to beproven.

7. Addition of probiotics to powderedinfant formulas has not been dem-onstrated to be harmful to healthyterm infants. On the other hand, ev-idence of clinical efficacy for theiraddition is insufficient to recom-mend the routine use of these for-mulas. No RCTs have directly com-pared the health benefits of feedinghuman milk versus infant formulasupplemented with probiotics.




8. Probiotics should not be given tochildren who are seriously orchronically ill until the safetyof administration has beenestablished.

9. Prebiotics may prove to be benefi-cial in reducing common infec-tions and atopy in otherwisehealthy children. However, confir-matory studies, especially in chil-dren fed formula that is not par-tially hydrolyzed, are neededbefore any recommendations canbe made.

10. Addition of oligosaccharides asprebiotics to infant formula is notunreasonable but lacks evidencedemonstrating clinical efficacy atthis time. Cost/benefit studies arealso necessary to support theiraddition to infant formulas.

11. Important questions remain in es-tablishing the clinical applicationsfor probiotics, including theoptimal duration of probiotic ad-ministration as well as preferredmicrobial dose and species. The

long-term impact on the gut micro-flora in children is unknown. It alsoremains to be established whetherthere is significant biological benefitin the administration of probioticsduring pregnancy and lactation,with direct comparison to potentialbiological benefit derived fromprobiotic-containing infant formu-las. Similar questions exist for theuse of prebiotics.

Appendix 1 contains examples of cur-rently available probiotic products andthe probiotic content of various func-tional foods in the United States. Thislist demonstrates the wide variation inprobiotic content in these products. In-formation about other probiotics canalso be found on aWeb site maintainedby industry (www.usprobiotics.org).

LEAD AUTHORSDan W. Thomas, MDFrank R. Greer, MD, Immediate PastChairperson

COMMITTEE ON NUTRITION,2009–2010Jatinder J. S. Bhatia, MD, ChairpersonSteven A. Abrams, MD

Stephen R. Daniels, MD, PhDMarcie Beth Schneider, MDJanet Silverstein, MDNicolas Stettler, MD, MSCEDan W. Thomas, MD

LIAISONSLaurence Grummer-Strawn, PhD – Centers forDisease Control and PreventionRear Admiral Van S. Hubbard, MD, PhD –National Institutes of HealthValérie Marchand, MD – Canadian PaediatricSocietyBenson M. Silverman, MD – Food and DrugAdministrationValery Soto, MS, RD, LD – US Department ofAgriculture

SECTION ON GASTROENTEROLOGY,HEPATOLOGY, AND NUTRITIONEXECUTIVE COMMITTEE, 2009–2010Leo A. Heitlinger, MD, ChairpersonRobert D. Baker Jr, MD, PhDDavid A. Gremse, MDRoberto Gugig, MDJenifer R. Lightdale, MD

FORMER EXECUTIVE COMMITTEEMEMBERSWilliam J. Byrne, MDWilliam J. Cochran, MDArthur R. Euler, MDMelvin B. Heyman, MD

STAFFDebra L. Burrowes, [email protected]

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APPENDIX 1 Selected Dietary Supplements

Product Active Ingredient CFU Count per Dose

VSL#3 S thermophilus, Bifidobacterium species,Lactobacillus species

450 billion, combined

Culturelle LGG 10 billionFlorastor S boulardii 5 billionGNC L acidophilus 1.6 billion

B bifidum 1.6 billionCVS brand L acidophilus, Bifidobacterium longum 1 billionNature Made L acidophilus 500 millionSelected functional foodsDannon Activia yogurt Bifidus regularis 100 000–1 million/gStonyfield Farm yogurt, refrigerated (not frozen) Lactobacillus bulgaricus, S thermophilus, L

acidophilus, Lactobacillus casei, L reuteri,Bifidus species

10 million/g, combined (throughout shelf-life)

Sweet acidophilus milk (Purity Dairy), refrigerated L acidophilus 4 million/mLKefir, refrigerated (Lifeway Foods) B lactis, Lactobacillus casei, L acidophilus,

Lactobacillus rhamnosus, Streptococcusdiacetylactis, L plantarum, Saccharomycesflorentinus, Leuconostoc cremoris, Blongum, B breve

20–40 million/mL

Nestle Good Start natural cultures B lactis 107/100 kcalMead Johnson Nutramigen with Enflora LGG LGG 107/100 kcal

CFU indicates colony-forming unit.



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http://thomas.loc.gov/cgi-bin/bdquery/z?d096:HR06940:@@@L&summ2=m&

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