Inflammatory bowel disease: lessons from the IL-10 gene-deficient mouse

The pathogenesis of Crohn's disease likely involves multifactorial interact ions between genetic factors and environmental triggers. The most recent st udies suggest that luminal bacteria are a significant factor in the onset a nd chronicity of inflammation. In interleukin-10 (IL-10) gene-deficient mic e a Crohn's-like colitis develops when the mice are raised under convention al animal care facilities but fails to develop when they are raised under g erm-free conditions. These mice demonstrate significant alterations in the species and the levels of bacteria colonizing the colon, suggesting that ge netic factors in the host may be critical in controlling bacterial coloniza tion. In addition, early treatment of IL-10 gene-deficient mice with antibi otics can prevent the development of colitis in later life, suggesting that early events during the neonatal period can influence later disease progre ssion. Recent work has focused on using probiotic bacterial mixtures to alt er the microbial balance in the colon in attempts to reduce inflammation. T he use of the VSL-3 probiotic mixture in the IL-10 gene-deficient mouse res ulted in a complete normalization of physiological transport function and b arrier integrity, in conjunction with a reduction in mucosal secretion of T NF-a and IFN-gamma. Further, it would appear that a soluble factor is relea sed from a bacterium found in the VSL-3 mixture that can act directly on th e epithelium to enhance barrier integrity. Results from animal models of in flammatory bowel disease suggest that genetically susceptible hosts can mou nt a pathogenic cellular immune response to specific nonpathogenic bacteria l species, as a consequence of defective immunologic tolerance and lack of appropriate mucosal defences. Probiotic bacteria appear to be a promising n ew alternative for the treatment of clinical conditions that are associated with alterations in gut barrier function, including Crohn's disease.