Gut Mucosal Microbiome of Patients With Low-Grade Adenomatous Bowel Polyps.

BACKGROUND AND AIMS: Colorectal cancer etiology is multifactorial and influenced by colonic environmental exposures leading to the accumulation of genetic lesions in precancerous polyps. There is growing recognition for a role of the gut microbiome in colorectal cancer progression, but the structure of the gut mucosal microbiome in the early stages of polyp growth is limited. The aim of this study was to characterize the gut mucosal microbiome from patients with low-grade conventional bowel neoplasia compared to symptomatic but polyp-free patients. METHODS: In this case-control study conducted at a tertiary referral hospital, 148 symptomatic patients undergoing colonoscopy were prospectively recruited. Mucosal biopsies adjacent to low-grade dysplasia (LGD) adenomatous polyps were used for 16S rRNA gene amplicon sequencing to define bacterial taxonomies relative to polyp-free controls. RESULTS: Minimal differences in gut mucosa community diversity measures were observed between participants with or without LGD adenomas. After correcting for clinical covariates, patients with adenomas in the proximal colon revealed elevated amplicons from Parabacteroides distasonis, Bacteroides uniformis, and unassigned Lachnospiraceae spp. Bacteroides/Phocaeicola massiliensis was the only microbe consistently found to be decreased in the gut mucosa of LGD adenoma patients compared with controls. Participants with LGD polyps in the distal colon showed more amplicons from Howardella sp. and Blautia faecicola. CONCLUSION: This study identified microbial candidates in the colonic mucosa that are associated with adenomatous LGD bowel neoplasia as an early step in the colorectal carcinogenesis pathway.