Re: Clinical Efficacy of Probiotics: Review of the Evidence With Focus on Children

Saavedra, Jose M MD; Yolken, Robert H MD

Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e31802fdab9
Letters to the Editor
Author Information

Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, MD Nestlé Nutrition Glendale, CA

Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, MD

Article Outline

To the Editor: We read with interest the Clinical Report recently published by the NASPGHAN Nutrition Report Committee on the topic of probiotics (1). The document is to be commended for its thoroughness in addressing the use of probiotics for various digestive and some systemic conditions. A few comments may help clarify or amplify certain aspects discussed in the Report.

The authors appropriately point out that “probiotics” are a widely heterogeneous group of microbes, with varying biological activities, and thus, “not all probiotics are created equal.” Indeed, stating that probiotics, in general, are “efficacious” or may raise safety concerns would be as inappropriate as stating that “antibiotics” in general are efficacious or may raise safety concerns.

The Clinical Report adequately describes efficacy documented for specific organisms, but safety is discussed in general for probiotics. Although implied in the Report, the explicit documentation of safety of the use of individual probiotic genera and its species for specific populations cannot be overemphasized. In addition, the Report states that available probiotics do not require oversight by health or government agencies. This is not universally the case. Examples that illustrate the efficacy, safety, and governmental regulatory issues mentioned above are Bifidobacteria and some specific Bifidobacteria species studied as probiotics.

Intestinal and fecal bacteria can be directly or indirectly a source of pathogens, particularly in young infants. Although yeasts and other genera of bacteria resident in the gut have been associated with systemic infections or other pathological conditions in infants, Bifidobacteria species have not, despite the fact that Bifidobacteria species constitute the majority (often 90%) of the intestinal biomass of a great number of young infants, particularly those who are breast-fed (2).

Lactobacilli, despite being consumed in large quantities in the food supply worldwide and residing in the intestine in large amounts, have only rarely been reported as being capable of causing disease. Even rarer are reports of infection linked to ingested Lactobacillus and Saccharomyces species used as probiotics. These rare cases typically occur in immunocompromised individuals. Currently, the greatest evidence of safe use in infants and children, including high-risk populations, has accumulated for Bifidobacteria species. B lactis, B longum, and other Bifidobacteria species have been increasingly used in various weaning foods, infant yogurts, and infant formulas worldwide, with no documented adverse effects. B lactis, in particular, is available worldwide, with approximately 1 million metric tons of yogurt containing B lactis cultures consumed annually. B lactis produces only L-lactate, with no risk of acidosis in infants, and infant formulas containing this organism have been commercialized worldwide for >15 years and consumed by millions of infants, with no reports of adverse effects. We have recently documented the safe long-term intake of varying doses of B lactis ingested by infants, with detailed documentation of viability and intake on a per-kilogram–body weight basis (3). B lactis, alone or in combination with other probiotics, has not shown adverse effects (and has shown some benefits) in prematurely delivered infants (4,5), healthy infants with diarrheal disease (6–10), infants receiving antibiotics (11), and infants born to mothers with HIV disease (12). Clearly, the degree of safety documentation of different probiotic genera and strains is varied and should guide their specific uses for specific target populations.

Regarding regulatory oversight; although the degree of oversight in terms of quality and claims is not ideal for probiotics sold as “supplements” in North America, the regulatory situation is different for probiotics in conventional foods, particularly when they are to be included in infant formulas—such as those used in some clinical trials cited in the Clinical Report. All infant formulas and their individual ingredients, including probiotics, undergo thorough regulatory scrutiny by the US Food and Drug Administration before they can be made commercially available in this country. To use the same example, the appropriateness of specific amounts of viable B lactis (strain Bb12) in infant formula has been exhaustively evaluated by the Food and Drug Administration (13). Formulas with this specific organism, and which follow strict quality control measures, can now be commercialized in the United States for use in healthy infants from birth.

As the Clinical Report correctly implies, probiotics are a concept and not a specific microbe in specific amounts with specific effects, benefits, and safety profiles, which is how each of these agents should be reported. A common approach to probiotic use has been as a “therapeutic” product, and often in a “supplement” or a “dose” in a capsule. Although this approach may have demonstrated varying degrees of efficacy for specific therapeutic purposes, the ultimate and probably most effective use of probiotic microbes may lie in their appropriate incorporation into foods, as functional components of our daily diet for general health maintenance and disease prevention, rather than as a new daily pill to fix a health-related problem. Only in this way do we have a realistic chance of modifying our modern, increasingly sterile environment, which appears to be associated with the growing epidemic of immune-related diseases (14).

Back to Top | Article Outline


1. Michail S, Sylvester F, Fuchs G, et al. Clinical efficacy of probiotics: review of the evidence with focus on children. J Pediatr Gastroenterol Nutr 2006; 43:550–557.
2. Yoshioka H, Iseki K, Fujita K. Development and differences of intestinal flora in the neonatal period in breast-fed and bottle-fed infants. Pediatrics 1983; 72:317–321.
3. Saavedra JM, Abi-Hanna A, Moore N, et al. Long-term consumption of infant formulas containing live probiotic bacteria: tolerance and safety. Am J Clin Nutr 2004; 79:261–267.
4. Mohan R, Koebnick C, Schildt J, et al. Effects of Bifidobacterium lactis Bb12 supplementation on intestinal microbiota of preterm infants: a double-blind placebo controlled randomized study. J Clin Microbiol 2006; 44:4025–4031.
5. Stratiki E, Sevastiadou S, Stamouli K, et al. The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants. Early Hum Devel 2007; DOI: 0.1016/j.earlhumdev.2006.12.02.
6. Chouraqui JP, Van Egroo LD, Fichot MC. Acidified milk formula supplemented with Bifidobacterium lactis: impact on infant diarrhea in residential care settings. J Pediatr Gastroenterol Nutr 2004; 38:288–292.
7. Sazawal S, Dhingra U, Sarkar A, et al. Efficacy of milk fortified with a probiotic Bifidobacterium lactis (DR-10TM) and prebiotic galacto-oligosaccharides in prevention of morbidity and on nutritional status. Asia Pac J Clin Nutr 2004; 13:S28.
8. Weizman Z, Asli G, Alsheikh A. Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents. Pediatrics 2005; 115:5–9.
9. Shamir R, Makhoul IR, Etzioni A, et al. Evaluation of a diet containing probiotics and zinc for the treatment of mild diarrheal illness in children younger than one year of age. J Am Coll Nutr 2005; 24:370–375.
10. Saavedra JM, Bauman NA, Oung I, et al. Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet 1994; 344:1046–1049.
11. Correa NB, Peret Filho LA, Penna FJ, et al. A randomized formula controlled trial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibiotic-associated diarrhea in infants. J Clin Gastroenterol 2005; 39:385–389.
12. Cooper PA, Mokhachane M, Bolton KD, et al. Growth of infants born from HIV positive mothers fed an acidifed starter formula containing Bifidobacterium lactis [abstract]. Eur J Pediatr 2006; 165(Suppl 13), 114.
13. US Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Food Additive Safety. Summary of All GRAS (Generally Recognized as Safe) Notices. GRAS Notice No. GRN 000049-Bifidobacterium lactis strain Bb12 and Streptococcus thermophilus strain Th4. Bethesda, MD: US Food and Drug Administration; June 14, 2000.
14. Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 2002; 347:911–920.
© 2007 Lippincott Williams & Wilkins, Inc.