Bifidobacterium lactis inhibits NF-kappaB in intestinal epithelial cells and prevents acute colitis and colitis-associated colon cancer in mice

Abstract

BACKGROUND: The aim of this study was to investigate the antiinflammatory effects of Bifidobacterium lactis on intestinal epithelial cells (IECs) and on experimental acute murine colitis and its tumor prevention effects on colitis-associated cancer (CAC) in mice.

METHODS: Human HT-29 cells were stimulated with IL-1beta, lipopolysaccharides, or tumor necrosis factor-alpha with and without B. lactis, and the effects of B. lactis on nuclear factor kappa B (NF-kappaB) signaling in IEC were examined. For in vivo study, dextran sulfate sodium (DSS)-treated mice were fed with and without B. lactis. Finally, we induced colonic tumors in mice by azoxymethane (AOM) and DSS and evaluated the effects of B. lactis on tumor growth.

RESULTS: B. lactis significantly suppressed NF-kappaB activation, including NF-kappaB-binding activity and NF-kappaB-dependent reporter gene expression in a dose-dependent manner, and suppressed IkappaB-alpha degradation, which correlated with the downregulation of NF-kappaB-dependent gene products. Moreover, B. lactis suppressed the development of acute colitis in mice. Compared with the DSS group, the severity of DSS-induced colitis as assessed by disease activity index, colon length, and histological score was reduced in the B. lactis-treated group. In the CAC model, the mean number and size of tumors in the B. lactis-treated group were significantly lower than those in the AOM group.

CONCLUSIONS: Our data demonstrate that B. lactis inhibits NF-kappaB and NF-kappaB-regulated genes in IEC and prevents acute colitis and CAC in mice. These results suggest that B. lactis could be a potential preventive agent for CAC as well as a therapeutic agent for inflammatory bowel disease.