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Using microorganisms to influence positively the course of an illness caused by injurious microorganisms is an approach with mounting clinical evidence showing efficacy. Whereas antibiotics will remain an important therapeutic option, there are limitations and problems to their increasing and chronic usage, and probiotics offer a strategy to reduce antibiotic usage. Increasingly, it has become clear that the mechanisms whereby probiotics can impact in intestinal diseases involve a large repertoire of responses. This review summarizes recent findings on how probiotics may effect benefit through interactions with host eukaryotic cells.Limiting the access of microbes associated with the development of disease to host mucosal surfaces and altering the responses of host to microbial insults are potential mechanisms whereby probiotics can influence the pathogenesis of disease. Evidence is accumulating that live, viable probiotic organisms diminish accessibility to intestinal epithelial cell; however, the mucosal exclusion is not through direct blockage of shared epithelial receptors between probiotic microbes and pathogenic organisms. Modulation of mucosal defenses such as innate protective mechanisms, enhanced epithelial cell survival, and immune responses have all been shown to have potential in aiding in these actions. Intestinal epithelial cell adherence influences response and, as such, appears to be necessary but may not be wholly sufficient, because soluble bacterial factors have been reported to effect modulation of immune and nonimmune responses of eukaryotic cells.There is a considerable repertoire of responses potentially responsible for the effects of probiotics, and these responses appear to involve a complex interplay between the microbes of the intestinal tract and the cells of the host. Continued work can be expected to further the understanding of the mechanisms involved, and more work is needed to determine the relative clinical importance of each of the phenomena. These studies are expected to help direct the most efficacious use of probiotics for inflammatory conditions arising from the intestinal tract.