Escherichia coli strains from patients with inflammatory bowel diseases have disease-specific genomic adaptations

Abstract

ObjectiveEscherichia coli is over-abundant in the gut microbiome of patients with IBD, yet most studies have focused on the adherent-invasive E. coli pathotype. Here, we aimed to identify IBD-specific or phenotype-specific genomic functions of diverse E. coli lineages. DesignWe investigated E. coli from patients with UC, CD and a pouch and healthy subjects. The majority of E. coli genomes were reconstructed directly from metagenomic samples, including publicly available and newly sequenced fecal metagenomes. Clinical metadata and biomarkers were collected. Functional analysis at the gene and mutation level and genome replication rates of E. coli strains were performed, and correlated with IBD phenotypes and biomarkers. ResultsOverall, 530 E. coli genomes were analysed. A specific E. coli lineage (B2) was more prevalent in UC compared to other IBD phenotypes. Genomic metabolic capacities varied across E. coli lineages and IBD phenotypes. Specifically, sialidases involved in host mucin utilization, were exclusively present in a single lineage and were depleted in patients with a pouch. In contrast, enzymes that hydrolyze inulin were enriched in patients with a pouch. E. coli from patients with UC were twice as likely to encode the genotoxic molecule colibactin than strains from patients with CD or pouch. Strikingly, patients with a pouch showed the highest E. coli growth rates, even in the presence of antibiotics. Fecal calprotectin did not correlate with the relative abundance of E. coli. Finally, we identified multiple IBD-specific loss-of function mutations in E. coli genes encoding for bacterial cell envelope and secretion components. ConclusionThis study presents E. coli as a commensal species better adapted to the overly-active mucosal immune milieu in IBD, that may benefit from intestinal inflammation, rather than causing it. The evidence given here suggests adaptive evolution toward attenuated virulence in some E. coli strains, coupled with a rapid growth despite the presence of antibiotics.