Use of Probiotics in Childhood Gastrointestinal Disorders

Abstract

Intestinal flora contain pathogenic micro-organisms, primarily in the large bowel; but most are benign, and some have advantageous effects. Altering enteric flora to modulate a gastrointestinal disease process is a concept that is gaining in popularity throughout the world. Several studies have recently been completed or are currently underway to evaluate the potential of this concept. This review summarizes the progress made in using probiotic bacteria in the treatment or prevention of pediatric gastrointestinal disorders. At birth, the gastrointestinal tract is sterile. Enteric flora are acquired during the newborn period and remain relatively stable throughout life. The primary source is maternal vaginal and fecal floras that are usually ingested at the time of delivery (1). There may also be some environmental acquisition, especially in infants born by cesarean delivery who do not have an opportunity to ingest maternal flora at delivery. Consequently, there may be some delay in acquisition of permanent flora by these infants (2). Once enteric bacterial flora have been established, it is fairly difficult to modify or change them permanently. Temporarily, flora may be modified negatively through the use of antibiotics or positively, through the introduction of desirable bacterial species into the gastrointestinal tract-that is, through the use of probiotics. Alternatively, nutrients(prebiotics) that stimulate the growth of certain favorable organisms, may be given to change flora in a positive way (3-6). Probiotics are defined as microorganisms, which, when ingested, may have a positive effect in the prevention and treatment of a specific pathologic condition (7). In contrast, Prebiotics are substances that, when ingested, promote the growth and establishment of beneficial micro-organisms (8,9). PROBIOTIC ORGANISMS Lactobacilli are perhaps among the most attractive of probiotics because of their longstanding use in fermentation of foods and historical record of safety (10,11). Lactobacillus is a diverse group of organisms that is part of a larger group of lactic acid bacteria-nonpathogenic gram-positive bacteria that produce lactic acid as a primary metabolic end product. Lactic acid bacteria include lactobacillus, lactococcus, streptococcus, and others. Lactobacilli, themselves, vary greatly from one species to another, often with different genetic makeup and different adherence and colonization patterns (12). Consequently, use of the term "lactobacillus" is meaningless when classifying probiotics; each particular lactobacillus species must be studied individually for its probiotic properties and ultimately for its beneficial clinical effects. In addition to lactobacillus, several other organisms have shown therapeutic potential, including a few species of Saccharomyces, a yeast, and additional bacteria, Bifidobacterium, andStreptococcus thermophilus (Table 1)(13). Many of the inconsistencies in studies in which probiotic organisms are evaluated for beneficial clinical effects are caused by the lack of specificity in selecting the species for study or by the inadequate identification or reporting of the species involved.TABLE 1: Some probiotic agents with existing clinical dataA probiotic should be innocuous. Broad consumption obviates the opportunity for distribution of potentially pathogenic organisms. Probiotics should act against pathogens by multiple mechanisms and should elicit minimal resistance to its effects (14). The organisms should also be capable of marshalling host defenses against potential pathogens. The onset of beneficial effects should be rapid in comparison with the several days to weeks required for a vaccine to become fully protective(15,16). Probiotics should function whether administered alone or with antibiotics. Most of the studies on probiotics have been performed using whole, live organisms (17). However, killed organisms or even components of organisms may be effective in stimulating immunologic reactions or even in inducing binding with certain compounds or structures within the gastrointestinal tract (18). In addition, probiotics may function by synthesizing certain compounds or producing metabolic by-products that could be protective or induce a positive effect. In this situation, these metabolic by-products may be used therapeutically(19,20). MECHANISMS OF ACTION Probiotics have several mechanisms of action (Table 2). For example, Lactobacillus casei subsp rhamnosus(Lactobacillus GG) produces compounds that inhibit the growth of several gram-positive and gram-negative bacteria(21,22). Examples include hydrogen peroxide and pyroglutamate (21). A few other lactobacilli are capable of producing similar substances. Short chain fatty acids are commonly produced (23). These lower the colonic pH, which favors the growth of organisms with less pathogenicity. Most of these data have been derived from studies in vitro, however; confirmation of these effects in vivo would be difficu