Liu Weixin, Lau Harry C H, Ding Xiao, Yin Xiaole, Wu William Ka Kei, Wong Sunny Hei, Sung Joseph J Y, Zhang Tong, Yu Jun
Institute of Digestive Disease and The Department of Medicine and Therapeutics State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong Hong Kong SAR China.
Environmental Microbiome Engineering and Biotechnology Laboratory, Center for Environmental Engineering Research, Department of Civil Engineering The University of Hong Kong Hong Kong SAR China.
Imeta. 2025 Mar 5;4(2):e70008. doi: 10.1002/imt2.70008. eCollection 2025 Apr.
Antimicrobial resistance is a major global health concern. However, the source of gut resistome remains unsolved. We aimed to analyze the contribution of environmental antimicrobial resistance genes (ARGs) to colorectal cancer (CRC) patients. Here, we collected metagenomic data from 1,605 human stool samples (CRC = 748; healthy = 857) and 1,035 city-matched environmental samples, in which 110 CRC, 112 healthy, and 56 environmental samples were newly collected. Compared to healthy subjects, CRC patients had significantly higher ARG burden ( < 0.01) with increased levels of multidrug-resistant ARGs. Gut ARGs in CRC also had a closer similarity to environmental ARGs ( < 0.001). By comparing environmental and gut ARGs, 28 environmental ARGs were identified as CRC-specific ARGs, including and , which were not identified in healthy subjects. Meanwhile, more mobile ARGs (mARGs) from the environment were observed in CRC patients compared to healthy subjects ( < 0.05). The hosts of mARGs were mainly pathogenic bacteria (e.g., () and ()). Compared to healthy subjects, CRC patients showed elevated horizontal gene transfer efficiency from the environment to gut. Consistently, the abundance of pathobionts carrying specific mARGs (e.g., and ) were significantly increased in CRC patients compared to healthy subjects ( < 0.05). We thus reveal a route of ARG dissemination from the environment into the gut of CRC patients.
抗菌药物耐药性是全球主要的健康问题。然而，肠道耐药基因组的来源仍未解决。我们旨在分析环境抗菌耐药基因（ARGs）对结直肠癌（CRC）患者的影响。在此，我们收集了1605份人类粪便样本（CRC = 748份；健康 = 857份）和1035份城市匹配环境样本的宏基因组数据，其中新收集了110份CRC、112份健康和56份环境样本。与健康受试者相比，CRC患者的ARG负担显著更高（<0.01），多重耐药ARGs水平升高。CRC中的肠道ARGs与环境ARGs也具有更密切的相似性（<0.001）。通过比较环境和肠道ARGs，鉴定出28种环境ARGs为CRC特异性ARGs，包括 和 ，在健康受试者中未鉴定到。同时，与健康受试者相比，在CRC患者中观察到更多来自环境的可移动ARGs（mARGs）（<0.05）。mARGs的宿主主要是病原菌（如 ()和 ()）。与健康受试者相比，CRC患者表现出从环境到肠道的水平基因转移效率升高。一致地，与健康受试者相比，携带特定mARGs（如 和 ）的致病共生菌丰度在CRC患者中显著增加（<0.05）。因此，我们揭示了ARG从环境传播到CRC患者肠道的途径。
