Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer.

Publication Title

Cell Host Microbe

Document Type

Article

Publication Date

10-13-2021

Keywords

washington; seattle; isb

Abstract

Colorectal cancer is a major health concern worldwide. Growing evidence for the role of the gut microbiota in the initiation of CRC has sparked interest in approaches that target these microorganisms. However, 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 polyp subtypes using sequencing and culturing techniques. We found a correlation between Bacteroides fragilis recovered and the level of inflammatory cytokines in the mucosa adjacent to the polyp. Additional analysis revealed that B. fragilis from patients with polyps are bft-negative, activate NF-κB through Toll-like receptor 4, induce a pro-inflammatory response, and are enriched in genes associated with LPS biosynthesis. This study provides fundamental insight into the microbial microenvironment of the pre-neoplastic polyp by highlighting strain-specific genomic and proteomic differences, as well as more broad compositional differences in the microbiome.

Clinical Institute

Cancer

Clinical Institute

Digestive Health

Specialty/Research Institute

Institute for Systems Biology

Specialty/Research Institute

Gastroenterology

Specialty/Research Institute

Oncology

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