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Although the gut microbiome is implicated in colorectal cancer (CRC), microbiome and metabolome alterations along the adenoma-carcinoma sequence remain unclear. Here, we profile stool metagenomes obtained from 354 women 12.1 ± 4.8 years following adenoma resection and from their 1:1-matched controls, as well as stool metabolomes from 184 pairs. Metagenomic profiles are compared with those from 14 independent CRC case-control studies. Microbial composition differs between adenoma cases and controls and agrees with CRC-associated alterations (Pearson’s rho = 0.26, p < 0.0001). Thirty-one microbes, including Faecalibacterium prausnitzii and Flavonifractor plautii , are altered in both conditions and correlate with lifestyle factors. Thirty metabolites and 7 sub-pathways, particularly sphingolipids, are associated with adenomas. Adenomas also exhibit disease-specific microbe-metabolite associations, including those between Bilophila wadsworthia and alanine-containing dipeptides. These findings reveal gut microbial and metabolomic alterations detectable years after adenoma resection, supporting the presence of an altered microbiome along the adenoma-CRC continuum.
Nogal et al. (Fri,) studied this question.