Paraclostridium tenue Exhibits Antitumor Activity Through Generating Antitumor Metabolites and Modulating Gut...

Colorectal cancer (CRC) is a digestive tract malignant tumor with a relatively high incidence and mortality rate worldwide. The occurrence and development of CRC are closely associated with disturbances in the gut microbiota. Paraclostridium tenue (synonym Eubacterium tenue) is generally considered a harmless commensal and can be isolated from fecal samples of healthy adults. However, whether this bacterium is a beneficial organism with an antitumor effect is unknown. This study systematically evaluated the anti-CRC effects of P. tenue strain Pt517 on CRC cells in vitro and in the CT26 syngeneic mouse model. Pt517 culture supernatant (Pt517CS) inhibited the proliferation, colony formation, and migration ability of CRC cells; induced cell apoptosis; and altered cell cycle distribution. Daily intragastric administration of Pt517 significantly inhibited tumor growth in mice; increased the expression levels of TNF-α, INF-γ, and CD8 in tumor tissues; and decreased the levels of IL-6, IL-10, and TGF-β. Pt517 intervention significantly modulated the gut microbiota composition with increased relative abundance of Parabacteroides goldsteinii, Lachnospiraceae, and Enterorhabdus caecimuris B7. The long-chain fatty acids (LCFAs), stearic acid and palmitic acid, were increased in the serum of treatment group mice and detected in Pt517CS. Functional verification indicated that stearic acid and palmitic acid directly inhibited the proliferation of CT26 cells in a dose-dependent manner, suggesting that Pt517 might exert its anti-CRC effect by secreting LCFAs. These findings indicate that P. tenue Pt517 is a potential new candidate for the microbial treatment of CRC, which warrants further validation for its safety and efficacy before clinical translation.