Escherichia coli Strains from Patients with Inflammatory Bowel Diseases have Disease-specific Genomic Adaptations

Vadim Dubinsky, Leah Reshef, Keren Rabinowitz, Nir Wasserberg, Iris Dotan, Uri Gophna*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Aims: Escherichia coli is over-abundant in the gut microbiome of patients with inflammatory bowel disease [IBD]. Here, we aimed to identify IBD-specific genomic functions of diverse E. coli lineages. Methods: We investigated E. coli genomes from patients with ulcerative colitis [UC], Crohn's disease [CD] or a pouch, and healthy subjects. The majority of genomes 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 with 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, whereas those involved in inulin hydrolysis were enriched in patients with a pouch. E. coli strains from patients with UC were twice as likely to encode the genotoxic molecule colibactin than strains from patients with CD or a 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 overactive mucosal immune milieu in IBD, rather than causing it. Our results reveal mutations that may lead to attenuated antigenicity in some E. coli strains.

Original languageEnglish
Pages (from-to)1584-1597
Number of pages14
JournalJournal of Crohn's and Colitis
Volume16
Issue number10
DOIs
StatePublished - 1 Oct 2022

Keywords

  • Escherichia coli
  • IBD
  • genomics

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