Triclosan (TCS) is a high-volume chemical used as an antimicrobial ingredient in more than 2000 consumer products, such as toothpaste, cosmetics, kitchenware, and toys. We report that brief exposure to TCS, at relatively low doses, causes low-grade colonic inflammation, increases colitis, and exacerbates colitis-associated colon cancer in mice. Exposure to TCS alters gut microbiota in mice, and its proinflammatory effect is attenuated in germ-free mice. In addition, TCS treatment increases activation of Toll-like receptor 4 (TLR4) signaling in vivo and fails to promote colitis in Tlr4^−/− mice. Together, our results demonstrate that this widely used antimicrobial ingredient could have adverse effects on colonic inflammation and associated colon tumorigenesis through modulation of the gut microbiota and TLR4 signaling. Together, these results highlight the need to reassess the effects of TCS on human health and potentially update policies regulating the use of this widely used antimicrobial.

Significance: Obesity is associated with enhanced colonic inflammation, which is a major risk factor for colorectal cancer. To date, the mechanisms by which obesity increases colonic inflammation are not well-understood, and there are few effective strategies for controlling obesity-induced colonic inflammation and associated diseases. Here, using LC-MS/MS–based metabolomics, we report that soluble epoxide hydrolase (sEH) could be a novel therapeutic target for obesity-induced colonic inflammation. This could lead to rapid human translation, as pharmacological inhibitors of sEH are being evaluated in human clinical trials targeting multiple disorders.