| Title: |
The Role of Fecal Microbiota in Liver Toxicity Induced by Perfluorooctane Sulfonate in Male and Female Mice. |
| Authors: |
Lilong Jiang1,2; Yanjun Hong1,2,3 hongyj7@mail.sysu.edu.cn; Pingting Xiao4; Xiaoxiao Wang1; Jinghui Zhang1; Ehu Liu4; Huijun Li4; Zongwei Cai1 zwcai@hkbu.edu.hk |
| Source: |
Environmental Health Perspectives. Jun2022, Vol. 130 Issue 6, p067009-1-067009-12. 12p. 3 Color Photographs, 3 Graphs. |
| Subject Terms: |
*Animal experimentation; *Fluorocarbons; Biological models; One-way analysis of variance; Hepatotoxicology; Feces; T-test (Statistics); Microbiota; Data analysis software; Mice |
| Abstract: |
BACKGROUND: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that can cause hepatotoxicity. The underlying toxicological mechanism remains to be investigated. Given the critical role of fecal microbiota in liver function, it is possible that fecal microbiota may contribute to the liver toxicity induced by PFOS. OBJECTIVES: We aimed to investigate the role of liver-fecal microbiota axis in modulating PFOS-induced liver injury in mice. METHODS: Male and female mice were exposed to PFOS or vehicle for 14 d. In this investigation, 16S rDNA sequencing and metabolomic profiling were performed to identify the perturbed fecal microbiota and altered metabolites with PFOS exposure. In addition, antibiotic treatment, fecal microbiota transplantation, and bacterial administration were conducted to validate the causal role of fecal microbiota in mediating PFOS-induced liver injury and explore the potential underlying mechanisms. RESULTS: Both male and female mice exposed to PFOS exhibited liver inflammation and steatosis, which were accompanied by fecal microbiota dysbiosis and the disturbance of amino acid metabolism in comparison with control groups. The hepatic lesions were fecal microbiota-dependent, as supported by antibiotic treatment and fecal microbiota transplantation. Mice with altered fecal microbiota in antibiotic treatment or fecal microbiota transplantation experiments exhibited altered arginine concentrations in the liver and feces. Notably, we observed sex-specific lower levels of key microbiota, including Lactobacillus, Enterococcus, and Akkermansia. Mice treated with specific bacteria showed lower arginine levels and lower expression of the phosphorylated mTOR and P70S6K, suggesting lower activity of the related pathway and mitigation of the pathological differences observed in PFOS-exposed mice. CONCLUSIONS: Our study demonstrated the critical role of the fecal microbiota in PFOS-induced liver injury in mice. We also identified several critical bacteria that could protect against liver injury induced by PFOS in male and female mice. Our present research provided novel insights into the mechanism of PFOS-induced liver injury in mice. [ABSTRACT FROM AUTHOR] |
| : |
Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
GreenFILE |