Jianan Zhang, Morgan E Walker, Katherine Z Sanidad, Hongna Zhang, Yanshan Liang, Ermin Zhao, Katherine Chacon-Vargas, Vladimir Yeliseyev, Julie Parsonnet, Thomas D Haggerty, Guangqiang Wang, Joshua B Simpson, Parth B Jariwala, Violet V Beaty, Jun Yang, Haixia Yang, Anand Panigrahy, Lisa M Minter, Daeyoung Kim, John G Gibbons, LinShu Liu, Zhengze Li, Hang Xiao, Valentina Borlandelli, Hermen S Overkleeft, Erica W Cloer, Michael B Major, Dennis Goldfarb, Zongwei Cai, Matthew R Redinbo, Guodong Zhang
Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut...
January 10, 2022: Nature Communications