Novel bacterium <i>Enterocloster</i> sp. M3 promotes colorectal tumorigenesis via the production of the carcinogen styrene

This study identifies M3 as a novel pro-tumorigenic bacterium in CRC, capable of direct biosynthesis of the carcinogenic metabolite styrene. We provide the first evidence of bacterial styrene biosynthesis, unveiling a previously unrecognized mechanism by which gut bacteria may promote colorectal tumorigenesis.<b>WHAT IS ALREADY KNOWN ON THIS TOPIC</b>The bacterial marker m3 has been associated with colorectal cancer, but the bacterium carrying it had not been cultured.Styrene is a recognized environmental carcinogen linked to cancers, and its bacterial biosynthesis had not been reported.<b>WHAT THIS STUDY ADDS</b>We isolated and characterized the novel bacterium M3, which carries the m3 marker. It is phylogenetically related to <i>Enterocloster aldenensis</i> but possesses distinct genetic and phenotypic features.M3 promotes colorectal tumorigenesis through the production of tumor-promoting metabolites, including styrene.Fecal styrene levels are significantly elevated in colorectal cancer patients.We elucidated the mechanism of direct styrene biosynthesis in M3, identifying two novel enzymes-aspartate ammonia-lyase and uroporphyrinogen decarboxylase-that catalyze this process.<b>HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY</b><i>M3 and bacterially derived styrene may serve as novel targets for colorectal cancer prevention and treatment strategies.</i>