Microbiota-mediated reactivation of triclosan oxidative metabolites in colon tissues

Hongna Zhang, Katherine Z. Sanidad, Jianan Zhang, Guangqiang Wang, Rong Zhang, Chengchen Hu, Yongfeng Lin, Thomas D. Haggerty, Julie Parsonnet, Yuxin Zheng, Guodong Zhang*, Zongwei Cai*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number130509
JournalJournal of Hazardous Materials
Volume445
Early online date28 Nov 2022
DOIs
Publication statusPublished - 5 Mar 2023

Scopus Subject Areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution
  • Health, Toxicology and Mutagenesis

User-Defined Keywords

  • Colon
  • Gut microbiota
  • Hydroxylation
  • Metabolism
  • Triclosan

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