Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer

Nat Commun. 2014 Sep 3:5:4724. doi: 10.1038/ncomms5724.


Enterobacteria, especially Escherichia coli, are abundant in patients with inflammatory bowel disease or colorectal cancer (CRC). However, it is unclear whether cancer is promoted by inflammation-induced expansion of E. coli and/or changes in expression of specific microbial genes. Here we use longitudinal (2, 12 and 20 weeks) 16S rRNA sequencing of luminal microbiota from ex-germ-free mice to show that inflamed Il10(-/-) mice maintain a higher abundance of Enterobacteriaceae than healthy wild-type mice. Experiments with mono-colonized Il10(-/-) mice reveal that host inflammation is necessary for E. coli cancer-promoting activity. RNA-sequence analysis indicates significant changes in E. coli gene catalogue in Il10(-/-) mice, with changes mostly driven by adaptation to the intestinal environment. Expression of specific genes present in the tumour-promoting E. coli pks island are modulated by inflammation/CRC development. Thus, progression of inflammation in Il10(-/-) mice supports Enterobacteriaceae and alters a small subset of microbial genes important for tumour development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Escherichia coli / genetics*
  • Escherichia coli / immunology
  • Escherichia coli / pathogenicity
  • Escherichia coli Infections / complications
  • Escherichia coli Infections / genetics*
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / pathology
  • Female
  • Gene Expression
  • Genes, Bacterial*
  • Genome, Bacterial*
  • Genomic Islands
  • Host-Pathogen Interactions
  • Inflammation / complications
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Male
  • Mice
  • Mice, Knockout
  • Microbiota / genetics
  • Microbiota / immunology
  • RNA, Ribosomal, 16S / genetics


  • IL10 protein, mouse
  • RNA, Ribosomal, 16S
  • Interleukin-10