Dataset Information

Triclocarban exposure exaggerates colitis and colon tumorigenesis: roles of gut microbiota involved.

ABSTRACT: Triclocarban (TCC) is a widely used antimicrobial ingredient in consumer products and is a ubiquitous contaminant in the environment. In 2016, the FDA removed TCC from over-the-counter handwashing products, but this compound is still approved for use in many other personal care products. A better understanding of its impact on human health could lead to significant impact for public health and regulatory policies. Here we show that exposure to low-dose TCC exaggerated the severity of colitis and exacerbated the development of colitis-associated colon tumorigenesis, via gut microbiota-dependent mechanisms. Exposure to TCC increased dextran sodium sulfate (DSS)- and interleukin 10 (IL-10) knockout-induced colitis, and exaggerated azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice. Regarding the mechanisms, TCC exposure reduced the diversity and altered the composition of gut microbiota and failed to promote DSS-induced colitis in mice lacking the microbiota, supporting that the presence of the microbiota is critical for the pro-colitis effects of TCC. Together, these results support TCC could be a novel risk factor for colitis and colitis-associated colon cancer, and further regulatory policies on this compound could be needed.

SUBMITTER: Yang H

PROVIDER: S-EPMC7524142 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Triclocarban exposure exaggerates colitis and colon tumorigenesis: roles of gut microbiota involved.

Yang Haixia H Sanidad Katherine Z KZ Wang Weicang W Xie Minhao M Gu Min M Cao Xiaoqiong X Xiao Hang H Zhang Guodong G

Gut microbes 20191124 1

Triclocarban (TCC) is a widely used antimicrobial ingredient in consumer products and is a ubiquitous contaminant in the environment. In 2016, the FDA removed TCC from over-the-counter handwashing products, but this compound is still approved for use in many other personal care products. A better understanding of its impact on human health could lead to significant impact for public health and regulatory policies. Here we show that exposure to low-dose TCC exaggerated the severity of colitis and ...[more]

PMID: 31760871

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Project description:There is growing evidence that individuals with colonic adenomas and carcinomas harbor a distinct microbiota. Alterations to the gut microbiota may allow the outgrowth of bacterial populations that induce genomic mutations or exacerbate tumor-promoting inflammation. In addition, it is likely that the loss of key bacterial populations may result in the loss of protective functions that are normally provided by the microbiota. We explored the role of the gut microbiota in colon tumorigenesis by using an inflammation-based murine model. We observed that perturbing the microbiota with different combinations of antibiotics reduced the number of tumors at the end of the model. Using the random forest machine learning algorithm, we successfully modeled the number of tumors that developed over the course of the model on the basis of the initial composition of the microbiota. The timing of antibiotic treatment was an important determinant of tumor outcome, as colon tumorigenesis was arrested by the use of antibiotics during the early inflammation period of the murine model. Together, these results indicate that it is possible to predict colon tumorigenesis on the basis of the composition of the microbiota and that altering the gut microbiota can alter the course of tumorigenesis. IMPORTANCE Mounting evidence indicates that alterations to the gut microbiota, the complex community of bacteria that inhabits the gastrointestinal tract, are strongly associated with the development of colorectal cancer. We used antibiotic perturbations to a murine model of inflammation-driven colon cancer to generate eight starting communities that resulted in various severities of tumorigenesis. Furthermore, we were able to quantitatively predict the final number of tumors on the basis of the initial composition of the gut microbiota. These results further bolster the evidence that the gut microbiota is involved in mediating the development of colorectal cancer. As a final proof of principle, we showed that perturbing the gut microbiota in the midst of tumorigenesis could halt the formation of additional tumors. Together, alteration of the gut microbiota may be a useful therapeutic approach to preventing and altering the trajectory of colorectal cancer.

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Dataset Information

Triclocarban exposure exaggerates colitis and colon tumorigenesis: roles of gut microbiota involved.

Publications

Triclocarban exposure exaggerates colitis and colon tumorigenesis: roles of gut microbiota involved.

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