Genomic and Functional Characterization of a Mucosal Symbiont Involved in Early-Stage Colorectal Cancer

Abstract

The rising incidence of colorectal cancer (CRC) is a major health concern worldwide, yet little is known about the composition and role of the microbiota associated with precancerous polyps. Here, we found distinct microbial signatures between patients with and without polyps and between the polyp sub-types using 16S rRNA sequencing and linear discriminate analysis. In parallel, we found a correlation between the amount of bft-negative Bacteroides fragilis recovered and the level of inflammatory cytokines in the mucosa adjacent to the polyp. Despite sharing a core genome, we found that B. fragilis from patients with polyps were enriched in LPS biosynthesis genes, activated nuclear factor kappa B through Toll-like receptor 4 and induce a robust pro-inflammatory response. Together, these data provide fundamental insight into the pre-neoplastic polyp microenvironment by highlighting the critical role that commensal bacteria play in the initiation of the inflammatory process.