Insights into a Possible Mechanism Underlying the Connection of Carbendazim-Induced Lipid Metabolism Disorder and Gut Microbiota Dysbiosis in Mice.

Carbendazim (CBZ), a systemic, broad-spectrum benzimidazole fungicide, is widely used to control fungal diseases and has been regarded as an endocrine disruptor that causes mammalian toxicity in different target organs. Here, we discovered that chronic administrations of CBZ at 0.2, 1, and 5 mg/kg body weight for 14 weeks not only changed the composition of gut microbiota but also induced significant increases in body, liver, and epididymal fat weight in mice. At the biochemical level, the serum triglyceride (TG) and glucose levels also increased after CBZ exposure. Moreover, the level of serum lipoprotein lipase (LPL), which plays an important role in fatty acid release from TG, was decreased significantly. For gut microbiota, 16S rRNA gene sequencing and real-time qPCR revealed that CBZ exposure significantly perturbed the mice gut microbiome, and gas chromatography found that the production of short-chain fatty acids were altered. Moreover, CBZ exposure increased the absorption of exogenous TG in the mice intestine and inhibited the TG consumption, eventually leading the serum triglyceride to maintain higher levels. The increase of lipid absorption in the intestine direct caused hyperlipidemia and the multi-tissue inflammatory response. In response to the rise of lipid in blood, the body maintains the balance of lipid metabolism in mice by reducing lipid synthesis in the liver and increasing lipid storage in the fat. Chronic CBZ exposure induced the gut microbiota dysbiosis and disturbed lipid metabolism, which promoted the intestinal absorption of excess triglyceride and caused multiple tissue inflammatory responses in mice.

Chronic exposure to fungicide propamocarb induces bile acid metabolic disorder and increases trimethylamine in C57BL/6J mice.

Propamocarb (PM) is a widely used fungicide that affects lipid biosynthesis in fungi. In this study, we explored the effects of PM on mouse metabolism and gut microbiota-related pathways by exposing C57BL/6J mice to 1, 3, and 10 mg/L PM through drinking water for a duration of 10 weeks. We found that hepatic bile acids (BAs) were considerably increased in the PM-treated group. The transcription of genes related to BA synthesis and transportation were also markedly altered in the liver and the ileum; accordingly, serous BA profiles were changed. BAs are tightly associated with energy metabolism and the gut microbiota; as expected, we observed that hepatic glycolysis; ß-oxidation; fatty acid transportation, release and synthesis; and triacylglycerol synthesis and transportation were significantly altered at the transcriptional level. Gut microbial community structures were significantly changed both in cecal contents and feces. Using Linear discriminant analysis Effect Size (LEfSe), we found that Chloroflexi, Bacteroidetes and Actinobacteria phyla; Prevotellaceae, Odoribacteraceae and Porphyromonadaceae families; and Butyricimonas, Oscillospira, Parabacteroides, Prevotella and Dorea genera enriched in PM-treated mice. Fecal metabolites involved in energy metabolism were likewise altered. In addition, the atherosclerosis-promoting molecule trimethylamine was significantly increased in feces, which induced a disturbance in the cardiac NO/NOS pathway and an increase in NF-κB transcriptional levels. Our findings indicated that chronic PM exposure induced disorders in enterohepatic metabolism and had potential to increase the risk of cardiovascular disease.

Effects of short term lead exposure on gut microbiota and hepatic metabolism in adult zebrafish.

Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that has been associated with a wide range of toxic effects in humans and environmental animals. Here, effects of short time exposure to 10 and 30 µg/L Pb on gut microbiota and hepatic metabolism were analyzed in adult male zebrafish. We observed that both 10 and 30 µg/L Pb increased the volume of mucus in the gut. At phylum level, the abundance of α-Proteobacteria decreased significantly and the abundance of Firmicutes increased significantly in the gut when treated with 30 µg/L Pb for 7 days. In addition, the 16S rRNA gene sequencing for V3-V4 region revealed a significant change in the richness and diversity of gut microbiota in 30 µg/L Pb exposed group. A more depth analysis, at the genus level, discovered that 52 gut microbes identified by operational taxonomic unit analysis were changed significantly in 30 µg/L Pb treated group. Based on GC/MS metabolomics analysis, a total of 41 metabolites were significantly altered in 30 µg/L Pb treatment group. These changed metabolites were mainly associated with the pathways of glucose and lipid metabolism, amino acid metabolism, nucleotide metabolism. In addition, we also confirmed that the transcription of some genes related to glycolysis and lipid metabolism, including Gk, Aco, Acc1, Fas, Apo and Dgat, decreased significantly in the liver of zebrafish when exposed to 30 µg/L Pb for 7 days. Our results observed that Pb could cause gut microbiota dysbiosis and hepatic metabolic disorder in zebrafish.