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

The Journal of Antibiotics volume 75, pages 341–353 (2022)Cite this article

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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.

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Acknowledgements

This study was supported by the grant from the National Natural Science Foundation of China (Grant No. 82073510) and Basic Research Project of Sichuan Province (Grant No. 2020YJ0232) to ZZ.

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  1. Department of Environmental and Occupational Health, Sichuan University West China School of Public Health and West China Fourth Hospital, Chengdu, 610041, Sichuan, China

    Donglei Sun, Chao Zuo, Wei Huang, Jingjing Wang & Zunzhen Zhang

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  1. Donglei Sun
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  2. Chao Zuo
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  3. Wei Huang
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ZZZ conceived and designed study. SDL, ZC, and WJJ performed research. SDL and HW analyzed data. SDL wrote the paper. ZZZ revised the paper. All authors read and approved the paper.

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Correspondence to Zunzhen Zhang.

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Sun, D., Zuo, C., Huang, W. et al. Triclosan targeting of gut microbiome ameliorates hepatic steatosis in high fat diet-fed mice. J Antibiot 75, 341–353 (2022). https://doi.org/10.1038/s41429-022-00522-w

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