Novel bacterium Enterocloster sp. M3 promotes colorectal tumorigenesis via the production of the carcinogen styrene

BACKGROUND: The bacterial marker 'm3' shows promise for the non-invasive diagnosis of colorectal cancer (CRC) and adenomas. However, the m3-harboring bacterium (M3) had not been successfully cultured. OBJECTIVE: This study aims to elucidate the functional mechanisms of M3 in CRC. DESIGN: . Bacterial and fecal metabolites were analyzed by untargeted LC-MS and targeted LC/GC-MS. RNA-seq profiled host gene expression altered by M3. Key enzymes were identified through whole-genome sequencing and proteomics. RESULTS: cultures and mouse models, a function not previously reported in bacteria. Importantly, styrene levels were significantly elevated in feces of CRC patients and exceeded WHO safety limit in mouse gut (12.5 vs. 7.7 μg/kg/d). Moreover, we identified novel bacterial enzymes-aspartate ammonia-lyase and uroporphyrinogen decarboxylase-that convert phenylalanine to styrene. CONCLUSIONS: 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.