Strengthening of the intestinal epithelial tight junction by Bifidobacterium bifidum

Epithelial barrier dysfunction has been implicated as one of the major contributors to the pathogenesis of inflammatory bowel disease. The increase in intestinal permeability allows the translocation of luminal antigens across the intestinal epithelium, leading to the exacerbation of colitis. Thus, therapies targeted at specifically restoring tight junction barrier function are thought to have great potential as an alternative or supplement to immunology-based therapies. In this study, we screened Bifidobacterium, Enterococcus, and Lactobacillus species for beneficial microbes to strengthen the intestinal epithelial barrier, using the human intestinal epithelial cell line (Caco-2) in an in vitro assay. Some Bifidobacterium and Lactobacillus species prevented epithelial barrier disruption induced by TNF-alpha, as assessed by measuring the transepithelial electrical resistance (TER). Furthermore, live Bifidobacterium species promoted wound repair in Caco-2 cell monolayers treated with TNF-alpha for 48 h. Time course 1 H-NMR-based metabonomics of the culture supernatant revealed markedly enhanced production of acetate after 12 hours of coincubation of B. bifidum and Caco-2. An increase in TER was observed by the administration of acetate to TNF-alpha-treated Caco-2 monolayers. Interestingly, acetateinduced TER-enhancing effect in the coculture of B. bifidum and Caco-2 cells depends on the differentiation stage of the intestinal epithelial cells. These results suggest that Bifidobacterium species enhance intestinal epithelial barrier function via metabolites such as acetate.