• Probiotics are defined by the World Health Organization as “live micro-organisms, which when administered in adequate amounts, confer a health benefit to the host.”
• Nonpathogenic Gram-positive and Gram-negative bacteria that comprise normal gut flora, as well as yeast, meet the definition of a probiotic.
• Probiotics are considered a dietary supplement, and are generally regarded as safe. The Center for Food Safety and Nutrition (CFSAN) provides guidelines for manufacturers of probiotics. Because probiotics are not regulated as biologic drug products by the FDA, clinicians must carefully evaluate the use of such agents.
• Probiotic organisms are similar to the bacteria commonly found in fermented food products, such as yogurt, sour cream, sauerkraut and buttermilk. Other probiotic formulations are identical to the organisms that colonize the gut.
• Commonly used probiotic supplements contain single organisms, including the following:
  • Bifidobacteria
  • Lactobacilli
  • Streptococci
  • E. coli
  • Enterococci
  • Bacilli
• Yeast, including Saccharomyces boulardii, may be in some probiotic formulations.
• Multistrain probiotics incorporate a combination of the above organisms in varying quantities.
• Multiple formulations of probiotic products are available in single-strain and multistrain preparations:
  • Probiotic organisms may be consumed as fermented dairy products or as supplements in the form of a capsule, tablet, or powder formulation.
  • Supplements provide a more consistent dose of probiotic organisms than food products.

Pathophysiology

• Probiotics, are hypothesized to exert their primary effects on the gut by re-establishing the intestinal microfloral balance, competing for receptor sites in the intestinal lumen and competing with pathogens for nutrients.
• The proposed immunomodulatory functions of probiotics include enhancing host immune defenses via strengthening tight junctions between intestinal enterocytes, increasing immunoglobulin A production, stimulating cytokines, and producing substances (e.g., arginine, glutamine and short-chain fatty acids) thought to secondarily act as protective nutrients.

DIAGNOSIS

• The selection of a single strain versus a multistrain probiotic product or a bacterial probiotic versus a yeast probiotic should be based upon the underlying indication and whether the probiotic is administered for treatment or prophylaxis.
• The following probiotics have been shown to be efficacious for the following indications:
  

  Probiotic	Indication
  Lactobacilli
  Infectious diarrhea
  Antibiotic associated diarrhea
  Atopic dermatitis
  Urogenital infections
  Saccharomyces
  Clostridium difficile associated diarrhea
  Combination therapy with lactobacilli, bifidobacteria, and streptococci
  Irritable bowel syndrome
  Pouchitis

• Efficacy with 1 probiotic strain or species does NOT imply that other strains will be equally efficacious.

General Measures

• The units of dosing of oral probiotics are colony forming units (CFU).
• Currently, there are no established dosing recommendations for children.
• Studies, to date, in adults have used oral doses of 1–10 billion CFUs per dose, with administration frequency ranging from twice daily to weekly.
• Practitioners have used 1/2 of the adult dose for children of average weight, and 1/4 of the adult dose for infants.
• There are no known reports of “toxicity” associated with probiotics in adults or children.

Patient Monitoring

• Currently available probiotic formulations are viable microorganisms and therefore have the potential to cause invasive infections in hosts who may have compromised mucosal epithelia.
• Case reports of bacteremia associated with bacterial probiotic administration emphasize that supplementation should be used with caution in children with indwelling central venous catheters, prolonged hospitalizations, and compromised gut mucosal integrity.
• Predisposition to invasive infections with probiotic organisms is an area of active investigation.
• An extremely low incidence of bacteremia has been observed with widespread use of probiotics in Finnish adults. To date, there have not been any adverse effects attributable to probiotic consumption in pregnant women taking a probiotic to prevent atopic dermatitis in their infants or in HIV-positive adults taking a probiotic to prevent diarrhea.

FOLLOWUP

• The use of probiotics is a developing field. Specific probiotics may be beneficial for certain indications and hosts, but not for all.
• The American Academy of Pediatrics (AAP) has not issued formal recommendations for the use of probiotics; however, it does support their use on a case-by-case basis among patients who may benefit from therapy.
• Probiotics have been shown to be efficacious in randomized, double-blind, placebo controlled studies for the following indications:
  • Decreasing the duration of infectious diarrheal episodes in pediatric inpatients, daycare attendees, and children with rotaviral infections in resource-poor areas.
• Reducing antibiotic-associated diarrhea in children receiving PO and IV antibiotics.
  • Treatment and prevention of pouchitis, inflammation of a surgically created distal small bowel reservoir, and irritable bowel syndrome in children and adults.
  • Treatment of atopic dermatitis (eczema)
• Other probiotic applications currently being evaluated include:
  • Prevention of necrotizing enterocolitis and maintenance of remission in persons with ulcerative colitis
  • Treatment and prevention of atopic disease other than eczema, including rhinitis and asthma
  • Improving tolerance of H. pylori eradication therapy
  • Prevention of genitourinary infections, such as UTIs and candidiasis
  • Prevention of dental caries
• Future investigations to evaluate the efficacy and safety of probiotics in large-scale, multicenter trials, to monitor the potency and composition of probiotic formulations, to develop in vitro and in vivo systems to understand the molecular mechanisms of action, and to understand the balance among infection, immunity and probiotics are in progress.
• The selection of a probiotic for pediatric use requires an understanding of the indication, the optimal formulation (single agent vs. multistrain), and the host.

FAQ

• Q: Isn’t yogurt just as effective as a probiotic supplement?
• A: Although probiotic organisms are found in some foods such as yogurt, the dosage of active organisms provided via routine consumption of yogurt may be inadequate for a therapeutic benefit. Food processing may result in variable viability and CFUs of probiotic organisms in yogurt, whereas there is less variability in the viability and CFUs in commercially-prepared probiotic formulations. Probiotic supplements offer a higher dose of organisms in a more concentrated form.The volume of yogurt that one would need to ingest to obtain the CFUs of a probiotic capsule or powder is significantly greater than an adult or child could consume in one serving.
• Q: What is the difference between probiotic and prebiotic supplements?
• A: Probiotic supplements contain live micro-organisms, while prebiotic supplements are substances that promote the growth of probiotic bacteria. The most common prebiotic supplements are fructo-oligosaccharides and galacto-oligosaccharides, which are found in human breast milk.

AUTHOR

Andi L. Shane, MD, MPH
Michael D. Cabana, MD, MPH

BIBLIOGRAPHY

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