Gut microbiota dysbiosis involves in host non-alcoholic fatty liver disease upon pyrethroid pesticide exposure

A growing body of evidence has demonstrated the significance of the gut microbiota in host health, while the association between gut microbiota dysbiosis and multiple diseases is yet elusive in the scenario of exposure to widely used pesticides. Here, we show that gut microbiota dysbiosis involves in host's abnormal lipid metabolism and consequently the non-alcoholic fatty liver disease in Xenopus laevis upon exposure to cis-bifenthrin, one of the most prevalent pyrethroid insecticides in the world. With the guidance of gut microbiota analysis, we found that cis-bifenthrin exposure significantly perturbed the gut microbial community, and the specific taxa that served as biomarkers were identified. Metabolomics profiling and association analysis further showed that a significant change of intestinal metabolites involved in lipid metabolic pathways were induced along with the microbiota dysbiosis upon exposure to cis-bifenthrin. Detailed investigation showed an altered functional regulation of lipids in the liver after cis-bifenthrin exposure and the accumulation of lipid droplets in hepatocytes. Specifically, a change in deoxycholic acid alters bile acid hepatoenteral circulation, which affects lipid metabolism in the liver and ultimately causes the development of fatty liver disease. Collectively, these findings provide novel insight into the gut microbiota dysbiosis upon pesticide exposure and their potential implication in the development of chronic host diseases related to liver metabolic syndrome.