Anti-tumor Mechanisms of Short-chain Fatty Acids, and the Relationship between the Gut Microbiome, Carcinogenesis, Tumor Growth, and Proliferation in Colorectal Carcinoma

Short-chain fatty acids (SCFAs) produced by the gut microbiome have been reported to have anti-tumor effects in several experimental systems [1-3]. Previously, we investigated the inhibitory effects of SCFAs (butyric acid, isobutyric acid, and acetic acid) on cell growth and proliferation in cultured human colorectal carcinoma (CRC) cell lines (DLD-1 cells, WirDr cells), and found that butyric acid displayed the strongest inhibitory effect [4]; however, the underlying mechanisms have not yet been elucidated. To investigate the anti-tumor mechanisms of SCFAs, we performed an in silico analysis of their inhibitory mechanism on tumor cell growth and proliferation in an experimental system in which SCFAs were added to cultured human CRC cell lines [5]; the results revealed that SCFAs suppress genes and transcription factors that participate in tumor cell growth, proliferation, and turnover, but do not affect genes involved in carcinogenesis, or genomes and factors associated with carcinogenic pathways.