Philip Sherman, M.D., FRCP(C), FAAP
Professor of Paediatrics, Microbiology & Dentistry
Hospital for Sick Children
University of Toronto
There is increasing interest in the role of probiotics for use in both promoting overall well-being, and as a prevention strategy in a variety of disease conditions. Probiotics are defined as live organisms that provide a benefit to human health. Randomized controlled trials support the role of selected probiotics as effective in the prevention of a variety of conditions affecting the intestinal tract including, for example, necrotizing enterocolitis in premature human infants. Probiotics have also been used with success as adjunctive therapy to enhance the efficacy of eradication of the gastric pathogen, Helicobacter pylori, while at the same time reducing the frequency of adverse effects arising when employing traditional medical treatment regimens.
We have demonstrated the efficacy of selected lactic acid-producing bacteria in preventing the consequences of damage induced by using a variety of complementary experimental models of gut injury including: enterohemorrhagic Escherichia coli O157:H7 infection of tissue culture epithelial cells, Citrobacter rodentium-induced colonic epithelial cell hyperplasia in mice, and stress-induced by both water aversion and maternal separation in rodents.
The precise mechanism of action of probiotics appears to depend on the strain, or combination of strains, under evaluation. Some probiotics affect integrity of the epithelial barrier, others impact on innate immune function of the host, while others increase adaptive immune responses, including increasing the number and activity of regulatory T cells recruited to the intestinal mucosa as a means of dampening inflammatory responses. Components of probiotics (so-called “pharmabiotics”), which can mediate beneficial effects, include surface-layer proteins, secreted proteins, exopolysaccharide, and DNA. “Designer probiotics” are genetically engineered to serve as a delivery vehicle to provide anti-inflammatory cytokines, receptor analogues, and immune regulatory molecules to the gut mucosa. These modified organisms have been employed with success in a variety of experimental models of gut injury, and are likely to provide an approach to developing novel interventions for use in both veterinary care settings and in the practice of clinical medicine in the near future.