TY - JOUR
T1 - Microbiota-mediated reactivation of triclosan oxidative metabolites in colon tissues
AU - Zhang, Hongna
AU - Sanidad, Katherine Z.
AU - Zhang, Jianan
AU - Wang, Guangqiang
AU - Zhang, Rong
AU - Hu, Chengchen
AU - Lin, Yongfeng
AU - Haggerty, Thomas D.
AU - Parsonnet, Julie
AU - Zheng, Yuxin
AU - Zhang, Guodong
AU - Cai, Zongwei
N1 - This research is supported by interdisciplinary faculty research award from the University of Massachusetts Amherst , USDA NIFA 2019–67017-29248 and 2020–67017-30844 , and USDA/Hatch MAS00556 (to G. Zhang); General Research Fund (12303319) of Hong Kong Research Grants Council (to Z. Cai); NIH/NIEHS R21 ES023371 (to J. Parsonnet); National Natural Science Foundation of China ( 82273591), and State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (KF2021–21) (to H. Zhang).
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2023/3/5
Y1 - 2023/3/5
N2 - 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.
AB - 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.
KW - Colon
KW - Gut microbiota
KW - Hydroxylation
KW - Metabolism
KW - Triclosan
UR - http://www.scopus.com/inward/record.url?scp=85143608070&partnerID=8YFLogxK
U2 - 10.1016/j.jhazmat.2022.130509
DO - 10.1016/j.jhazmat.2022.130509
M3 - Journal article
C2 - 36463744
AN - SCOPUS:85143608070
SN - 0304-3894
VL - 445
JO - Journal of Hazardous Materials
JF - Journal of Hazardous Materials
M1 - 130509
ER -