Perfluorooctanoic acid-induced liver injury is potentially associated with gut microbiota dysbiosis

Abstract

Perfluorooctanoic acid (PFOA), an environmental pollutant, is widely engaged in industrial products and tends to accumulate in the liver. Emerging evidence has suggested that the gut microbiome is a pivotal player in maintaining animal health and can potentially altered by xenobiotic. However, few studies explored whether PFOA-induced liver injury is associated with gut microbiota dysbiosis. In the present study, the effects of subacute and subchronic PFOA exposure on liver and gut microbiota in C57BL/6J mice were investigated. Our findings showed that both subacute and subchronic exposure to PFOA induced the liver inflammation, disrupted antioxidative homeostasis and caused liver histological abnormalities with detectable hepatomegaly, ultimately triggering liver injury. Besides, 16S rRNA sequencing analysis revealed that subacute PFOA exposure caused significant changes in the abundances of intestinal flora known to contribute to liver inflammation and oxidative stress, such as the Dehalobacterium and Bacteroides genera. Exposure to subchronic toxicity mainly induced the decrease in commensal probiotics including Lactobacillus and Bifidobacterium genera, which are potentially beneficial to liver damage, compared with that in the untreated group. They also resulted in disturbed functional capabilities of the microbial communities by a Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. Additionally, the levels of short-chain fatty acids (SCFAs), especially butyric acid, were significantly reduced by PFOA administration. Collectively, our observations suggested that liver damage induced by both subacute and subchronic PFOA exposures probably partly related to the gut microbiota dysbiosis and provided a new insight into the role of PFOA in liver injury.