Microbiota-mediated reactivation of triclosan oxidative metabolites in colon tissues.
Microbiota-mediated reactivation of triclosan oxidative metabolites in colon tissues.
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DOI：
10.1016/j.jhazmat.2022.130509
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发表时间：
2022-11
影响因子：
13.6
通讯作者：
Hongna Zhang;Katherine Z. Sanidad;Jianan Zhang;Guangqiang Wang;Rong Zhang;Chengchen Hu;Yongfeng Lin;T. Haggerty;J. Parsonnet;Yuxin Zheng;Guodong Zhang;Z. Cai
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文献类型：
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作者：
Hongna Zhang;Katherine Z. Sanidad;Jianan Zhang;Guangqiang Wang;Rong Zhang;Chengchen Hu;Yongfeng Lin;T. Haggerty;J. Parsonnet;Yuxin Zheng;Guodong Zhang;Z. Cai
三氯生（TCS）是一种广泛使用的抗菌剂，与许多不良健康结果相关。其肠道毒性已归因于肠道微生物介导的分子修饰，但TCS衍生物在肠腔中的微生物转化仍在很大程度上未知。芳香族羟基化是TCS的主要氧化代谢途径，与其在宿主组织中的毒性作用有关。在这里，我们的目的是揭示羟基-TCS（OH-TCS）在结肠中的生物学命运，肠道微生物主要居住在那里。与通过宿主代谢产生的谱不同，来自队列研究的人粪便中的OH-TCS物质保持未结合。通过跟踪小鼠肠道中的分子组成，在结肠直肠和粘膜中观察到游离形式的OH-TCS丰度升高，而结合形式的丰度降低。使用驱虫处理和无菌小鼠，以及体外方法，我们证明了肠道微生物编码的酶有效地将宿主代谢产生的葡糖苷酸/硫酸盐结合的OH-TCS转化回结肠组织中的生物活性游离形式。因此，提出了TCS衍生物的宿主-肠道微生物群代谢相互作用。这些结果揭示了微生物代谢在TCS毒性中的关键作用，并强调了将肠道微生物转化纳入环境化学品健康风险评估的重要性。
Triclosan (TCS) is a widespread antimicrobial agent that is associated with many adverse health outcomes. Its gut toxicity has been attributed to the molecular modifications mediated by commensal microbes, but microbial transformations of TCS derivatives in the gut lumen are still largely unknown. Aromatic hydroxylation is the predominant oxidative metabolism of TCS that linked to its toxicological effects in host tissues. Here, we aimed to reveal the biological fates of hydroxyl-TCS (OH-TCS) in the colon, where intestinal microbes mainly reside. Unlike the profiles generated via host metabolism, OH-TCS species remain unconjugated in human stools from a cohort study. Through tracking molecular compositions in mouse intestinal tract, elevated abundance of free-form OH-TCS while reduced abundance of conjugated forms was observed in the colon digesta and mucosa. Using antibiotic-treated and germ-free mice, as well as in vitro approaches, we demonstrate that gut microbiota-encoded enzymes efficiently convert glucuronide/sulfate-conjugated OH-TCS, which are generated from host metabolism, back to their bioactive free-forms in colon tissues. Thus, host-gut microbiota metabolic interactions of TCS derivatives were proposed. These results shed light on the crucial roles of microbial metabolism in TCS toxicity, and highlight the importance of incorporating gut microbial transformations in health risk assessment of environmental chemicals.