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

Cell Host Microbe. 2021 Oct 13;29(10):1589-1598.e6. doi: 10.1016/j.chom.2021.08.013. Epub 2021 Sep 17.


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.

Keywords: Bacteroides fragilis; colon cancer; colorectal polyp; inflammation; innate immunity; microbiome; microbiota.

MeSH terms

  • Aged
  • Bacteroides fragilis / classification
  • Bacteroides fragilis / genetics*
  • Bacteroides fragilis / isolation & purification*
  • Bacteroides fragilis / physiology
  • Colonic Polyps / immunology
  • Colonic Polyps / microbiology
  • Colonic Polyps / pathology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / microbiology*
  • Colorectal Neoplasms / pathology
  • Cytokines / genetics
  • Cytokines / immunology
  • Female
  • Gastrointestinal Microbiome
  • Genome, Bacterial
  • Genomics
  • Humans
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Phylogeny
  • Symbiosis


  • Cytokines