<i>Escherichia coli</i> strains from patients with inflammatory bowel diseases have disease-specific genomic adaptations

Abstract Background and Aims Escherichia coli is over-abundant in the gut microbiome of patients with IBD. Here, we aimed to identify IBD-specific genomic functions of diverse E. coli lineages. Methods We investigated E. coli genomes from patients with UC, CD or a pouch and healthy subjects. The majority of which were reconstructed from metagenomic samples, including newly sequenced faecal metagenomes. Clinical metadata were collected. Functional analysis at the gene and mutation level were performed and integrated with IBD phenotypes and biomarkers. Results Overall, 530 E. coli genomes were analysed. The E. coli B2 lineage was more prevalent in UC compared to other IBD phenotypes. Genomic metabolic capacities varied across E. coli lineages and IBD phenotypes. Host mucin utilisation enzymes were present in a single lineage and depleted in patients with a pouch, while those involved in inulin hydrolysis 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 inferred E. coli growth rates, even in the presence of antibiotics. Faecal calprotectin did not correlate with the relative abundance of E. coli. Finally, we identified multiple IBD-specific non-synonymous mutations in E. coli genes encoding for bacterial cell envelope components. Conclusions Comparative genomics indicates that E. coli is a commensal species adapted to the overly-active mucosal immune milieu in IBD, rather than causing it. Our results reveal mutations that may lead to attenuated antigenicity in some E. coli strains.