Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv, Israel.
Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel.
J Crohns Colitis. 2022 Nov 1;16(10):1584-1597. doi: 10.1093/ecco-jcc/jjac071.
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.
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.
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.
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.
大肠杆菌在炎症性肠病（IBD）患者的肠道微生物组中过度丰富。在这里，我们旨在确定不同大肠杆菌谱系的 IBD 特异性基因组功能。
我们研究了溃疡性结肠炎[UC]、克罗恩病[CD]或袋状结肠患者以及健康受试者的大肠杆菌基因组。大多数基因组是从宏基因组样本中重建的，包括新测序的粪便宏基因组。收集临床元数据。在基因和突变水平上进行功能分析，并与 IBD 表型和生物标志物相结合。
总体而言，分析了 530 个大肠杆菌基因组。与其他 IBD 表型相比，大肠杆菌 B2 谱系在 UC 中更为普遍。大肠杆菌谱系和 IBD 表型的基因组代谢能力存在差异。宿主粘蛋白利用酶存在于单一谱系中，在袋状结肠患者中耗尽，而参与菊粉水解的酶在袋状结肠患者中丰富。与 CD 或袋状结肠患者相比，UC 患者的大肠杆菌菌株更有可能编码遗传毒性分子 colibactin。值得注意的是，即使存在抗生素，袋状结肠患者的大肠杆菌生长速度仍然最高。粪便钙卫蛋白与大肠杆菌的相对丰度无关。最后，我们在编码细菌细胞包膜成分的大肠杆菌基因中鉴定出多个 IBD 特异性非同义突变。
比较基因组学表明，大肠杆菌是一种适应于 IBD 过度活跃的黏膜免疫环境的共生物种，而不是导致其发生的原因。我们的结果揭示了可能导致某些大肠杆菌菌株抗原性减弱的突变。
