Date on Senior Honors Thesis

5-2022

Document Type

Senior Honors Thesis

Degree Name

B.A.

Department

Biology

Degree Program

College of Arts and Sciences

Author's Keywords

PCB; Microbiome; Gut-Liver Axis; Sex-dependent

Abstract

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that have been associated with fatty liver disease, cardiovascular diseases, and other metabolic dysfunctions. Our laboratory group previously demonstrated that exposures to PCBs led to sex-dependent liver outcomes with female mice showing higher susceptibility to PCB- induced liver toxicity. Some of the underlying mechanisms driving these sex-dependent outcomes that were identified included PCB-modulated endocrine disruption. However, the PCB effects on the gut microbiome and the gut liver axis have not been investigated. Therefore, the objective of the current study is to identify PCB-induced changes in the gut microbiome and identify if this could be a cause for the observed sex-dependent PCB toxicity. Male and female C57BL6 mice were exposed to a mixture of PCBs for two weeks; cecal and ileal samples were isolated at euthanasia. 16S sequencing was performed and RT-PCR was used to examine ileal gene expression. The metagenomics results demonstrated significant sex differences in bacterial composition with PCB-exposed female mice exhibiting the lowest alpha diversity. In terms of beta diversity, there was a predominant sex effect driving the differences while PCB effects were subtler in both sexes. Additionally, assessment of ileal gene expression demonstrated that the PCB- exposed female mice had lower expression for genes encoding gut barrier proteins, namely Cldn2 and Muc2. With regards to inflammatory responses, PCB-exposed female mice showed decreased gene expression for the antimicrobial peptide, namely Tff3, thereby implicating an unhealthy mucosal environment. Taken together, the results demonstrated that PCB exposure impacted the gut microbiome and gut function in a sex-dependent manner, thus confirming the existence of sex differences on gut microbiota with environmental exposures. Future studies will include identification of key bacterial phyla that were altered with sex and exposure and correlating them with hepatic toxicity endpoints.

Lay Summary

Polychlorinated biphenyls (PCBs) are hazardous substances found in the environment that have been linked to a variety of health problems in people who are exposed to them. Liver disease, reproductive abnormalities, and cardiovascular illnesses are among the health consequences. While extensive studies have been done using experimental models to investigate PCB-mediated organ damage and toxicity, little is known about how PCBs behave in terms of their harmful effects in the context of sex and gender. The goal of the proposed study is to understand how pollutants like PCBs can alter the composition of gut bacteria, how these changes affect liver health, and whether these changes are different in males and females. This research will help us determine the association between different environmental pollutants with sex and gender, as well as identify if men or women are more susceptible to PCB-related health effects.

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