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Author ORCID Identifier

https://orcid.org/0000-0002-2689-3826

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2019

Month Degree Awarded

September

First Advisor

Guodong Zhang

Subject Categories

Animal Experimentation and Research | Biochemistry | Cancer Biology | Cell Biology | Microbiology | Pharmacology, Toxicology and Environmental Health

Abstract

Inflammatory bowel disease (IBD) has become a serious health problem since the incidence and prevalence of IBD has dramatically increased throughout the world. There is evidence that environmental factors are primarily responsible for the increase of IBD, therefore, it is important to identify novel environmental risk factors to reduce the risk of IBD and its associated diseases. Antimicrobials used in consumer products might serve as environmental risk factors for IBD and its associated diseases. Triclosan (TCS), triclocarban (TCC), benzalkonium chloride (BAC), benzethonium chloride (BET), and chloroxylenol (PCMX) are widely used antimicrobial ingredients in consumer products and are ubiquitous contaminants in the environment. In 2016, the FDA removed TCS and TCC from over-the-counter handwashing products while allowing additional time to develop new safety and efficacy data for BAC, BET, and PCMX. Therefore, it is important and timely to better understand the effects of these antimicrobials on human health. Currently, there not much known about how chronic exposure to low-dose consumer antimicrobials affects gut health. Here, using various in vitro and animal models, we found that: 1) TCS is metabolically re-activated in the gut by the actions of gut microbiota, leading to the accumulation of microbiota-derived toxic metabolites in the colon and resulting in gut-specific toxicity; 2) exposure to low-dose TCC exaggerated the severity of colitis and exacerbated the development of colitis-associated colon tumorigenesis, via gut microbiota-dependent mechanisms; and 3) exposure to low doses of BAC, BET, and PCMX, increases dextran sodium sulfate (DSS)-induced colonic inflammation and exposure to BAC increases azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice. Together, these results support that chronic exposure to consumer antimicrobials could be a novel risk factor for colitis and colitis-associated colon cancer through gut microbiota-dependent mechanisms. A better understanding of the impact antimicrobials on human health, specifically gut health, could lead to significant influence on public health and regulatory policies.

Available for download on Tuesday, September 01, 2020

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