Toll-Like Receptor 2-Mediated Suppression of Colorectal Cancer Pathogenesis by Polysaccharide A From Bacteroides fragilis

Abstract

The beneficial role of gut microbiota in intestinal diseases has been highlighted recently. Bacteroides fragilis found in the human gastrointestinal tract is a well-studied example of a beneficial bacterium that protects against intestinal inflammation. Polysaccharide A (PSA) from B. fragilis induces the production of interleukin (IL)-10 from immune cells via Toll-like receptor 2 (TLR2) signaling in animal colitis models. The direct effect of PSA on human colorectal cancer (CRC) cells has not been studied. Here, we report the effect of PSA from B. fragilis on CRC pathogenesis in SW620 and HT29 CRC cells and the molecular signaling underlying these effects. We demonstrated that PSA induced the production of the pro-inflammatory cytokine, IL-8, but not IL-10, in CRC cells. PSA inhibited CRC cell proliferation by controlling the cell cycle and impaired CRC cell migration and invasion by suppressing epithelial mesenchymal transition. Moreover, as in the case of other animal intestinal diseases, the protective role of PSA against CRC pathogenesis was also mediated by TLR2. Our results reveal that PSA from B. fragilis plays a protective role against CRC via TLR2 signaling.