Premium
Gut Microbiota‐Mediated Colonic Metabolism of Triclosan Contributes to its Proinflammatory Effects
Author(s) -
Sanidad Katherine Zabala,
Yang Jun,
Zhao Ermin,
Zhang Jianan,
Yang Haixia,
Xiao Hang,
Zhang Guodong
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb18
Subject(s) - gut flora , proinflammatory cytokine , colitis , triclosan , inflammation , microbiology and biotechnology , biology , chemistry , immunology , medicine , pathology
Triclosan (TCS) is an antimicrobial ingredient used in thousands of consumer products. Because of its widespread use, TCS causes ubiquitous contamination in the environment and is one of the top‐ten pollutants found in rivers in the United States. We have recently shown that exposure to TCS, at doses relevant to human exposure, can enhance colonic inflammation and colitis‐associated colon tumorigenesis in mice, suggesting that TCS could be a risk factor for these diseases. We also showed that the promoting effect of TCS on colonic inflammation requires gut microbiota since TCS failed to promote colonic inflammation in germ‐free mice. However, the functional roles of gut microbiota in the proinflammatory effects of TCS are unknown; in addition, the specific gut bacteria involved are also unknown. In this study, we examined the metabolism of TCS in C57BL/6 mice and the role of the gut microbiota in TCS metabolism in the colon using LC/MS‐MS analysis. Our results show that in the small intestine of mice treated with TCS via the diet there were elevated levels of TCS‐glucuronide (TCS‐G) and TCS‐sulfate (TCS‐S) while in the colon there were elevated levels of free‐form TCS. However, when the mice were treated with antibiotics, to deplete gut microbiota, prior and during exposure to TCS, there were elevated levels of TCS‐G and TCS‐S in the colon instead of free‐form TCS. This suggests that gut microbiota are responsible for the deconjugation of TCS‐G and TCS‐S to free‐form TCS in the colon. Using in vitro fermentation, we were able to identify specific bacteria responsible for the deconjugation of TCS‐conjugates to free‐form TCS. In addition, we then exposed MC38 mouse colon cancer cells to TCS, TCS‐G, or TCS‐S at a dose mimicking their levels in the colon. Our results showed that TCS, not TCS‐G or TCS‐S, increased the expression of the proinflammatory cytokines and chemokines. In summary, our results suggest that the gut microbiota are responsible for the metabolism of TCS in the colon which contributes to the proinflammatory effects of TCS. Our results also suggest that TCS could exaggerate disease development via gut microbiota and suggests potential adverse effects of antimicrobials on gut health. Further studies are needed to characterize the impact of TCS on gut diseases. Support or Funding Information This research is supported by a new faculty start‐up funding from UMass‐Amherst (to G.Z.). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .