A common antimicrobial additive increases colonic inflammation and colitis-associated colon tumorigenesis in mice

Sci Transl Med. 2018 May 30;10(443):eaan4116. doi: 10.1126/scitranslmed.aan4116.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Infective Agents / adverse effects*
  • Carcinogenesis / pathology*
  • Colitis / complications*
  • Colitis / microbiology
  • Colitis / pathology
  • Colon / microbiology
  • Colon / pathology*
  • Colonic Neoplasms / chemically induced*
  • Colonic Neoplasms / microbiology
  • Colonic Neoplasms / pathology
  • Dextran Sulfate
  • Disease Models, Animal
  • Gastrointestinal Microbiome / drug effects
  • Inflammation / chemically induced*
  • Inflammation / microbiology
  • Inflammation / pathology
  • Male
  • Metabolome
  • Mice, Inbred C57BL
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism
  • Triclosan / adverse effects

Substances

  • Anti-Infective Agents
  • Toll-Like Receptor 4
  • Triclosan
  • Dextran Sulfate