Structure of the Mucosal and Stool Microbiome in Lynch Syndrome

The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosal biopsies. A classifier leveraging stool metatranscriptomes resulted in modest power to predict interval development of preneoplastic colonic adenoma. Predictive transcripts corresponded with a shift in flagellin contributors and oxidative metabolic microenvironment, potentially factors in local CRC pathogenesis. This suggests that the effectiveness of prospective microbiome monitoring for adenomas may be limited but supports the potential causality of these consistent, early microbial changes in colonic neoplasia. [Display omitted] •Gut microbial changes in Lynch adenoma resemble later stage CRC with smaller effect•Colectomy with CRC history represented the largest effect on the Lynch microbiome•Feces metatranscriptome weakly predicted future preneoplastic adenoma development The gut microbiome has been linked to colorectal cancer (CRC). Here, Yan et al. use metagenomic and metatranscriptomic sequencing of feces integrated with 16S rRNA sequencing of colon biopsies in Lynch syndrome. They assess microbiome changes prior to colorectal neoplasia and determine potential causality of early microbial changes in CRC.