Metabolic Alteration of Gut Microbiota Is Associated With Host Non-alcoholic Fatty Liver Disease Induced by Pyrethroid in Xenopus Laevis

Abstract

Background: There is increasing awareness of the significance of the gut microbiome to host health, and a clear relationship has been established between the perturbed gut microbiome and multiple diseases. Cis-bifenthrin, a widely used agricultural pyrethroid insecticide, has been implicated as a cause of hepatotoxicity due to the oxidative stress produced during its metabolism by the liver. Studies have demonstrated the role of gut microbiota in gut-liver axis, it is possible that the perturbation of gut microbiota may also contribute to the toxicity of cis-bifenthrin on the liver.Results: 16S rRNA gene sequencing suggested that cis-bifenthrin exposure significantly perturbed the gut microbiota composition, and metabolomics analysis showed signature metabolic shifts arising from exposure. Moreover, we also found altered functional regulation of lipids in the liver after cis-bifenthrin exposure, and the accumulation of lipid droplets in hepatocytes was observed.Conclusions: Our results suggested cis-bifenthrin exposure disturbed the gut microbiota community and metabolite profile in frogs. Specifically, changes in bile acid metabolites altered bile acid hepatoenteral circulation, which affected lipid metabolism in the liver and ultimately caused the development of fatty liver disease. Our findings reveal novel insights into gut microbiota-host axis in frogs, and the perturbed microbial function provides novel mechanism contributing to cis-bifenthrin-induced toxicity.