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PEDIATRICS Vol. 109 No. 5 May 2002, pp. 956-958

COMMENTARY

Probiotics in Pediatrics

At birth, the gastrointestinal tract is sterile. Within hours, bacteria ingested during the birthing process rapidly colonize the gut. The gastrointestinal tract soon contains about 10 times as many bacteria as there are cells in the body. Hundreds of species are present, many of which are unculturable and remain unidentified. It is these bacteria that are responsible for priming the gastrointestinal immune system. Studies in germ-free mice have proven that without these bacteria, the systemic immune system will not function normally.¹

After this initial colonization, a person’s individual gut flora remain remarkably constant throughout life. The gut immune system learns to recognize and tolerate those bacterial species acquired during early infancy. Consequently, it is very difficult to permanently change gastrointestinal flora after this time. As one would therefore expect, each person’s bacterial flora are remarkably similar to that of his/her mother, as they were initially ingested from the mother’s vagina at birth. The vagina is typically colonized with normal fecal flora.²

Most gastrointestinal organisms are relatively benign. Some are potentially more pathogenic; however, many are actually beneficial. It is these beneficial organisms that have attracted attention as possible probiotics. Probiotics are defined as live microorganisms that, when ingested, produce some therapeutic or preventive health benefit.³ Because of the difficulty in permanently changing intestinal flora, successful colonization with a probiotic is usually transient. In fact, many so-called probiotics fail to colonize even transiently, as the gastrointestinal tract has many defenses that inhibit colonization. These include gastric acid, duodenal bile, mucin, and the gut immune system.⁴ Successful probiotics are capable of resisting these insults, and transiently take up residence in the gut. By definition, they also must be of human origin and have some demonstrable health promoting benefits proven by clinical studies.

It would seem logical that most health promoting benefits of probiotic organisms would be seen in disorders of the gastrointestinal tract. Certainly, mostly clinical studies have involved either the treatment or prevention of gastrointestinal disorders. Perhaps the disorder most thoroughly studied is acute diarrhea in children. Lactobacillus rhamnosus GG, for example, has been shown to significantly reduce the severity and duration of acute viral enteritis.⁵ Comparable findings have been demonstrated with Lactobacillus reuteri.⁶ It is interesting to note that, at least in the case of Lactobacillus GG, these benefits are not observed in the prevention or treatment of bacterial enteritis.⁷ Certain probiotics organisms also have some preventative role, reducing the risk of acquisition of viral gastroenteritis. Lactobacillus GG and certain strains of bifidobacteria have been shown to reduce the risk of diarrheal disease in high-risk population groups in both hospital and free-living environments.^8–10

Diarrhea is a common complication of antibiotic therapy, especially in children using broad-spectrum agents. Lactobacillus GG has been shown to reduce the risk of antibiotic associated diarrhea by approximately 75% in children in studies both in United States and Finland.^11–12 One study in adults failed to confirm this finding, however.¹³ As the dosage used in this adult study was lower on a per kilogram basis than in the pediatric studies, it is possible that the lack of effect in adults was related to a lower dosage. It is also possible that antibiotic associated diarrhea in adults is a distinctly different problem. Another biotherapeutic agent, so-called because it is a live organism although it is not human derived, is Saccharomyces boulardii. This yeast has been shown to reduce the risk of antibiotic-associated diarrhea in adults.¹⁴ Both S boulardii and Lactobacillus GG have demonstrated efficacy in the prevention of relapsing Clostridium difficile diarrhea.^15–16 The data, however, is much stronger for S boulardii.

Treatment of inflammatory disorders of the gastrointestinal tract with probiotics is an exciting new area of exploration. Animal studies have demonstrated that certain lactobacillus strains have protective immunomodulatory and bowel flora manipulating effects.¹⁷ Recently, a probiotic preparation containing several different microorganisms, has been successfully used to maintain remission in pouchitis. This condition is characterized by inflammation of a surgically created small bowel reservoir, commonly constructed after colectomy for ulcerative colitis.¹⁸ An open-labeled trial of Lactobacillus GG in children with Crohn’s disease has suggested some beneficial effect in reducing intestinal permeability and disease activity.¹⁹ A large, multicentered study is underway to confirm these findings. Because of the association of various forms of arthritis with bacterial disease,²⁰ there has been some speculation about the use of probiotics in rheumatoid arthritis as well. At present, no such studies have been conducted.

Perhaps the area most intriguing at the present time is the use of probiotics for immune regulation. It appears that at least some probiotics may be capable of both down-regulating the allergic response and in enhancing immune response against potential pathogens. For example, Lactobacillus GG has been shown to increase the antibody response to rotavirus infection and rotavirus vaccine.²¹ It has also been shown to enhance the antibody response to adults given typhoid vaccine when compared with comparably vaccinated adults receiving placebo.²² The potential beneficial effects of this immune enhancement is exemplified by a study showing that a group of children with cystic fibrosis treated with Lactobacillus GG had a reduced incidence of severe respiratory infections when matched with a comparable group of placebo-treated controls.²³

Alternatively, recent studies from Finland have demonstrated a reduced incidence of milk allergy in toddlers given Lactobacillus GG during early infancy.²⁴ Likewise, treatment of milk allergic toddlers with Lactobacillus GG seems to ameliorate both the extent and the severity of allergic eczema.²⁵ Down-regulation of the allergic response would seem unlikely in consideration of the immune-enhancing properties of this particular probiotic. However, this probiotic seems to be capable of redirecting the immune system from an allergic to a pathogen directed response. Early exposure to multiple pathogens has a similar effect as has been observed in infants who attend day care.²⁶

Probiotics have traditionally been thought to work by competitive exclusion.²⁷ These bacteria bind with the same receptors on the gut epithelium through which some pathogens normally gain access to the gut, the first step in translocation. In all likelihood, some probiotic effects are probably mediated in this manner. However, actual redirection of the gut and systemic immune response has been shown to result from probiotic administration.²⁸ It seems that certain organisms are capable of modifying the TH1 and TH2 lymphocytes, thereby altering the cytokine profile. TH2 cells are known to produce many cytokines involved in the allergic response. Probiotics also seem capable of enhancing the acquisition of tolerance to food protein antigens, an important step in the prevention of food allergy. In addition, some probiotics seem to be capable of altering or enhancing gut mucin secretion.^29,30 Mucin is important in acting as a barrier to invasion of the gut epithelium by pathogens. Additional studies will need to be conducted to explain all of these recently described findings. Nonetheless, it seems that probiotics may have the capacity to positively impact a number of infectious and inflammatory disease states in children.

CONCLUSION

The beneficial effects of probiotics seem to be strain-specific. For example, a few strains of certain species of lactobacillus may be capable of shortening the duration of rotavirus diarrhea, whereas most others are not.³¹ The genetic variability among various strains of lactobacilli is considerable.³² Probiotic benefits are most often dependent on the ability of the organism to colonize the bowel. This usually requires the presence of receptors on the bacterial cell wall that permit attachment to the gastrointestinal epithelium.³³ Most strains do not have such receptors. Certain strains are more bile- and acid-resistant than others and some strains produce bacteriocins, which kill adjacent organisms.³⁴ Additional factors or characteristics are probably also important. Consequently, controlled studies are needed to determine the efficacy of each specific strain of probiotic to determine its usefulness in clinical situations. Ultimately, we may view probiotics as we now view antibiotics, with many choices of strains useful in different situations and many double-blind, placebo-controlled studies to direct our choice for prevention or therapy.

Jon A. Vanderhoof, MD and Rosemary J. Young, RN, MS

University of Nebraska Medical Center
Section of Pediatric Gastroenterology and Nutrition
Omaha, NE 68198-5160

FOOTNOTES

Received for publication Feb 19, 2002; Accepted Feb 19, 2002.

Reprint requests to (J.A.V.) Departments of Pediatrics and Internal Medicine, University of Nebraska Medical Center, 985160 Nebraska Medical Center, Omaha, NE 68198-5160

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PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Vanderhoof, J. A. Articles by Young, R. J. Search for Related Content PubMed PubMed Citation Articles by Vanderhoof, J. A. Articles by Young, R. J. Related Collections Nutrition & Metabolism Related AAP Red Book topics: Clostridium difficile Social Bookmarking                         What's this?