A gut butyrate-producing bacterium Butyricicoccus pullicaecorum regulates short-chain fatty acid transporter and receptor to reduce the progression of 1,2-dimethylhydrazine-associated colorectal cancer.

Abstract

Gut microbes influence tumor development and progression in the intestines and may provide a novel paradigm for the treatment of colorectal cancer (CRC). Gut dysbiosis may be associated with the development and progression of CRC. Identifying the interactions between the colonic tract and gut microbiota may provide novel information relevant to CRC prevention. The present study examined the effects of butyrate-producing Butyricicoccus pullicaecorum (B. pullicaecorum) on mice with 1,2-dimethylhydrazine (DMH)-induced CRC and the microbial metabolite of B. pullicaecorum on CRC cells. Immunohistochemical staining of the mouse colon tissues and reverse transcription PCR of CRC cells were used to determine the protein and mRNA expression levels of the short-chain fatty acid (SCFA) transporter solute carrier family 5 member 8 (SLC5A8) and G-protein-coupled receptor 43 (GPR43). In CRC-bearing mice fed B. pullicaecorum, DMH-induced CRC regressed, body weight increased and serum carcinoembryonic antigen levels decreased. Notably, SLC5A8 and GPR43 were diffusely and moderately to strongly expressed in the neoplastic epithelial cells and underlying muscularis propria in the colons of the mice. In conclusion, administration of B. pullicaecorum or its metabolites improved the clinical outcome of CRC by activating the SCFA transporter and/or receptor. These results indicated that B. pullicaecorum was a probiotic with anti-CRC potential.