Oral Exposure of Mice to Carbendazim Induces Hepatic Lipid Metabolism Disorder and Gut Microbiota Dysbiosis

Toxicol Sci. 2015 Sep;147(1):116-26. doi: 10.1093/toxsci/kfv115. Epub 2015 Jun 11.


Carbendazim (CBZ) has been considered as an endocrine disruptor that caused mammalian toxicity in different endpoints. Here, we revealed that oral administrations with CBZ at 100 and 500 mg/kg body weight for 28 days induced hepatic lipid metabolism disorder which was characterized by significant increases of hepatic lipid accumulation and triglyceride (TG) levels in mice. The serum cholesterol (TC), high-density lipoprotein, and low-density lipoprotein levels also increased after CBZ exposure. Correspondingly, the relative mRNA levels of some key genes related to lipogenesis and TG synthesis increased significantly both in the liver and fat. Moreover, the increase in serum IL-1β and IL-6 levels by the treatment of CBZ indicated the occurring of inflammation. Furthermore, the levels of bioaccumulation of CBZ in the liver and gut were very low as compared in the feces, indicating that most of CBZ stayed in gastrointestinal tract and interacted with gut microbiota until excreted. At phylum level, the amounts of the Bacteroidetes decreased significantly in the feces after 5 days CBZ exposure. High throughput sequencing of the 16S rRNA gene V3-V4 region revealed a significant reduction in richness and diversity of gut microbiota in the cecum of CBZ-treated mice. UniFrac principal coordinates analysis observed a marked shift of the gut microbiota structure in CBZ-treated mice away from that of the controls. More deeply, operational taxonomic units' analysis identified that a total of 361 gut microbes were significant changed. In CBZ-treated groups, the relative abundance of Firmicutes, Proteobacteria, and Actinobacteria increased and that of Bacteroidetes decreased. Our findings suggested that CBZ could lead hepatic lipid metabolism disorder and gut microbiota dysbiosis in mice.

Keywords: carbendazim; gut microbiota; hepatic lipid metabolism disorder; inflammation; mice..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteroidetes / drug effects
  • Benzimidazoles / toxicity*
  • Carbamates / toxicity*
  • Cytokines / metabolism
  • Endocrine Disruptors / toxicity*
  • Feces / microbiology
  • Fungicides, Industrial / toxicity*
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / microbiology*
  • Lipid Metabolism / drug effects*
  • Lipogenesis / drug effects
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • RNA, Messenger / biosynthesis
  • Triglycerides / metabolism


  • Benzimidazoles
  • Carbamates
  • Cytokines
  • Endocrine Disruptors
  • Fungicides, Industrial
  • RNA, Messenger
  • Triglycerides
  • carbendazim