The probiotic approach to the treatment of gastrointestinal disease remains controversial and will remain so until the mechanisms through which probiotic bacterial strains antagonize pathogenic organisms or exert other beneficial effects in the host are fully understood through well-planned scientific study. Furthermore, there are significant differences between probiotic bacterial genera and species. It is crucial that each strain be tested on its own or in products designed for a specific function. Much research is directed toward understanding the mechanisms of action of oral probiotics. The main areas being examined are receptor competition, whereby probiotics compete with microbial pathogens for a limited number of receptors present on the surface epithelium; probiotic release of antimicrobial compounds; probiotic-induced increased levels of mucin secretion, which acts to block pathogen binding to epithelial receptors; probiotic bacterial ‘priming’ of gut-associated lymphoid tissue; and immunomodulation of gut-associated lymphoid and epithelial tissue response. Probiotics are able to enhance the activity of the intestinal immune system through the stimulation of macrophage and natural killer cells, the proliferation of lymphocytes and the increase of secretory immunoglobulin A production, although the specificity of the secretory immunoglobulin A production was unknown. Selected strains of probiotics are able to alter mucosal and systemic immune function at many levels, including stimulating mucosal production of interleukin-10 and producing systemic T helper 2 reponses. However, it remains to be proven which, if any, of these mechanisms have a clinical benefit or how they alter the pathophysiology of gastrointestinal diseases. With regard to the pathophysiology of inflammatory bowel disease, one of the most widely accepted theories is that the inflammation results from a dysregulation of the immune system to normal gut flora. Thus, common probiotic species may contribute to chronic inflammation. However, in several animal models, not all gut microflora cause the same degree of inflammation. Indeed, there are several reports demonstrating that probiotic species tend to down-regulate pro-inflammatory cytokine release rather than stimulate secretion. Thus, while it is possible that some probiotic strains may contribute to chronic inflammation, some of the strains may actively suppress inflammation.
Once protective mechanisms are understood, it will be possible to identify bacterial species as possessing certain beneficial traits, and optimal doses, timing of administration and potential synergy between bacterial species can then be determined. Several studies have shown that concentrations of endogenous Lactobacillus and Bifidobacterium species are decreased during active Crohn’s disease, ulcerative colitis and pouchitis. Leading from these findings is the speculation that the ratio of protective to harmful luminal bacteria may be involved in the determination of mucosal homeostasis, and that restoring microbial balance through antibiotic, probiotic and prebiotic approaches may be a true physiological approach to the treatment of gastrointestinal disease.