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

Abstract

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 tumor-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 tumor development.