Triclosan targeting of gut microbiome ameliorates hepatic steatosis in high fat diet-fed mice

Abstract

Antibiotic use provides a promising strategy for the treatment of non-alcoholic fatty liver disease (NAFLD) by regulating the gut microbiota composition. Triclosan, a widely used antibiotic, may improve gut microbiome dysbiosis associated with NAFLD through the suppression of pathogenic gram-negative bacteria. However, the effects of triclosan on gut microbiota and hepatic steatosis and have not been explored in NAFLD mouse model. In this study, C57BL/6J mice were fed with high fat diet (HFD) for continuous 20 weeks and treated with triclosan at 400 mg/kg/d for 8 weeks from week 13. We explored the effects of triclosan on hepatic lipid accumulation and gut microbiome in HFD-fed mice by histological examination and 16 S ribosomal RNA sequencing, respectively. Analysis on the composition of gut microbiota indicated that triclosan suppressed pathogenic gram-negative bacteria, including Helicobacter, Erysipelatoclostridium and Citrobacter, and increased the ratio of Bacteroidetes/Firmicutes in HFD-fed mice. Meanwhile, triclosan increased the relative abundance of beneficial gut microbiomes including Lactobacillus, Bifidobacterium and Lachnospiraceae, which protected against metabolic abnormality. The results of alpha-diversity and beta-diversity also showed the improvement of triclosan on bacterial diversity and richness in HFD-fed mice. Pathway analysis further confirmed that triclosan can regulate nutrient and energy metabolism through the elimination of deleterious bacteria. As a result, triclosan intervention significantly reduced lipid accumulation and alleviated hepatic steatosis in HFD-fed mice. In conclusion, our results suggest that triclosan can alleviate liver steatosis in HFD-fed mice by targeting the gut microbiome.