Association of distinct microbial signatures with premalignant colorectal adenomas.

Environmental exposures are a major risk factor for developing colorectal cancer, and the gut microbiome may serve as an integrator of such environmental risk. To study the microbiome associated with premalignant colon lesions, such as tubular adenomas (TAs) and sessile serrated adenomas (SSAs), we profiled stool samples from 971 participants undergoing colonoscopy and paired these data with dietary and medication history. The microbial signatures associated with either SSA or TA are distinct. SSA associates with multiple microbial antioxidant defense systems, whereas TA associates with a depletion of microbial methanogenesis and mevalonate metabolism. Environmental factors, such as diet and medications, link with the majority of identified microbial species. Mediation analyses found that Flavonifractor plautii and Bacteroides stercoris transmit the protective or carcinogenic effects of these factors to early carcinogenesis. Our findings suggest that the unique dependencies of each premalignant lesion may be exploited therapeutically or through dietary intervention.
Competing Interests: Declaration of interests R.J.X. is a co-founder of Celsius Therapeutics and Jnana Therapeutics, a member of the scientific advisory board of Nestle, and a member of the board of directors at Moonlake Immunotherapeutics. J.L.W.J. is a co-founder of AMILI and serves as a member of the scientific advisory board. D.C.C. is a consultant to Guardant. H.K. has received grant funding from Pfizer and is a consultant to Takeda. K.S. has served as a consultant to Arena, Boston Pharmaceutics, Gelesis, GI Supply, and Takeda/Shire; he has received research support from Ironwood and Urovant.
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