研究人员建立了一个管线，可系统地评估来自炎症性肠病患者的大量肠道共生菌的遗传毒性。研究人员确定了来自不同系统的分离物，它们的代谢物会造成DNA损伤，并发现了一个独特的基因毒素家族，即由结肠直肠癌（CRC）相关物种Morganella morganii生产的indolimine。一种不产生indolimine的M. morganii突变体缺乏遗传毒性，并且不能加剧小鼠结肠肿瘤的发生。
这些研究揭示了微生物组中存在着以前未曾探索过的基因毒性小分子，它们可能影响宿主在平衡和疾病中的生物学。
据悉，引起DNA损伤的微生物群代谢物可导致CRC。然而，自身肠道微生物产生的全部基因毒性化学物仍有待定义。
附：英文原文
Title: Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites
Author: Yiyun Cao, Joonseok Oh, Mengzhao Xue, Won Jae Huh, Jiawei Wang, Jaime A. Gonzalez-Hernandez, Tyler A. Rice, Anjelica L. Martin, Deguang Song, Jason M. Crawford, Seth B. Herzon, Noah W. Palm
Issue&Volume: 2022-10-28
Abstract: Microbiota-derived metabolites that elicit DNA damage can contribute to colorectal cancer (CRC). However, the full spectrum of genotoxic chemicals produced by indigenous gut microbes remains to be defined. We established a pipeline to systematically evaluate the genotoxicity of an extensive collection of gut commensals from inflammatory bowel disease patients. We identified isolates from divergent phylogenies whose metabolites caused DNA damage and discovered a distinctive family of genotoxins—termed the indolimines—produced by the CRC-associated species Morganella morganii. A non–indolimine-producing M. morganii mutant lacked genotoxicity and failed to exacerbate colon tumorigenesis in mice. These studies reveal the existence of a previously unexplored universe of genotoxic small molecules from the microbiome that may affect host biology in homeostasis and disease.
DOI: abm3233
Source: https://www.science.org/doi/10.1126/science.abm3233