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Sex-dependent modulation of PCB-mediated toxicity from a proteomic and microbiome perspective
Richa Singhal1,2, Zayna Qaissi3, Hao Zheng4
1Center for Cardiometabolic Science, University of Louisville, Louisville, KY, 40202, USA.
Scientific Reports
|November 14, 2025
Summary
Sex differences in polychlorinated biphenyl (PCB) toxicity are linked to distinct liver proteome and gut microbiome changes. This study reveals how PCBs impact males and females differently, highlighting gut-liver interactions in PCB toxicity.
Area of Science:
- Environmental Toxicology
- Hepatology
- Microbiome Research
Background:
- Polychlorinated biphenyls (PCBs) are persistent organic pollutants with known sex-dependent liver toxicity.
- Existing mechanisms inadequately explain these sex differences, necessitating investigation into gut-liver axis involvement.
Purpose of the Study:
- To investigate sex-specific alterations in the hepatic proteome and gut microbiome induced by PCB exposure.
- To determine the contribution of gut-liver interactions to sex-specific PCB toxicity.
Main Methods:
- Exposure of male and female C57BL/6J mice to Aroclor1260 and PCB126.
- Analysis of hepatic proteome using LC/MS and gut microbiome composition via 16S sequencing.
- Computational analysis of aryl hydrocarbon receptor (AHR) and liver-X-receptor (LXR) activation.
Main Results:
- Biological sex was a primary driver of hepatic proteome differences and PCB liver responses.
- PCB-exposed females showed increased hepatic AHR targets (e.g., CD36) and enhanced AHR/LXR activation.
- PCB-exposed males exhibited distinct gut microbiome shifts (increased Dehalobacterium) and reduced gut barrier gene expression.
Conclusions:
- PCB toxicity exhibits significant sex-specific patterns, involving distinct hepatic and gut microbiome alterations.
- Females display altered proteomic profiles related to AHR and LXR pathways.
- Males show more pronounced gut microbiome changes and compromised gut barrier integrity, underscoring the role of gut-liver interactions in PCB toxicity.
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