Vitamin C and vitamin D3 alleviate metabolic-associated fatty liver disease by regulating the gut microbiota and bile acid metabolism via the gut-liver axis

Qingling Chen; Lili Zhao; Ling Mei; Xiaotong Zhao; Ping Han; Jie Liu; Chao Meng; Ruifang Li; Rui Zhong; Kai Wang; Jia Li

doi:10.3389/fphar.2023.1163694

Vitamin C and vitamin D₃ alleviate metabolic-associated fatty liver disease by regulating the gut microbiota and bile acid metabolism via the gut-liver axis

Front Pharmacol. 2023 Apr 5:14:1163694. doi: 10.3389/fphar.2023.1163694. eCollection 2023.

Authors

Qingling Chen^{1

2}, Lili Zhao², Ling Mei^{1

2}, Xiaotong Zhao³, Ping Han^{1

2}, Jie Liu², Chao Meng³, Ruifang Li⁴, Rui Zhong⁵, Kai Wang⁶, Jia Li²

Affiliations

¹ Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China.
² Department of Gastroenterology and Hepatology, Tianjin Second People's Hospital, Tianjin, China.
³ Department of Clinical Laboratory, Tianjin Second People's Hospital, Tianjin, China.
⁴ School of Medicine, Nankai University, Tianjin, China.
⁵ Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin, China.
⁶ Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.

Abstract

Background: Previous studies have demonstrated that both vitamin C (VC) and vitamin D₃ (VD₃₎ have therapeutic potential against metabolic disorders, including obesity, diabetes, and metabolic-associated fatty liver disease (MAFLD). However, it is unclear whether VC supplementation is associated with improving the intestinal flora and regulating the metabolism of bile acids via the gut-liver axis in MAFLD. There is still no direct comparison or combination study of these two vitamins on these effects. Methods: In this study, we employed biochemical, histological, 16S rDNA-based microbiological, non-targeted liver metabolomic, and quantitative real-time polymerase chain reaction analyses to explore the intervening effect and mechanism of VC and VD₃ on MAFLD by using a high-fat diet (HFD)-induced obese mouse model. Results: Treatment of mice with VC and VD₃ efficiently reversed the characteristics of MAFLD, such as obesity, dyslipidemia, insulin resistance, hepatic steatosis, and inflammation. VC and VD₃ showed similar beneficial effects as mentioned above in HFD-induced obese mice. Interestingly, VC and VD₃ reshaped the gut microbiota composition; improved gut barrier integrity; ameliorated oxidative stress and inflammation in the gut-liver axis; inhibited bile acid salt reflux-related ASBT; activated bile acid synthesis-related CYP7A1, bile acid receptor FXR, and bile acid transportation-related BSEP in the gut-liver axis; and improved bile secretion, thus decreasing the expression of FAS in the liver and efficiently ameliorating MAFLD in mice. Conclusion: Together, the results indicate that the anti-MAFLD activities of VC and VD₃ are linked to improved gut-liver interactions via regulation of the gut microbiota and bile acid metabolism, and they may therefore prove useful in treating MAFLD clinically.

Keywords: bile acid metabolism; gut microbiota; gut-liver axis; metabolic-associated fatty liver disease; vitamin C; vitamin D3.

Grants and funding

The present work was supported by the Natural Science Foundation of Tianjin City (20JCYBJC01150) and the Tianjin Health Science and Technology Project (No. TJWJ2021MS034, No. TJWJ2021QN063, and No. TJWJ2021ZD010).