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

TITLE=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

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1163694

DOI=10.3389/fphar.2023.1163694

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Previous studies have demonstrated that both vitamin C (VC) and vitamin D<sub>3</sub> (VD<sub>3)</sub> 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 <italic>via</italic> the gut-liver axis in MAFLD. There is still no direct comparison or combination study of these two vitamins on these effects.</p><p><bold>Methods:</bold> 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 VD<sub>3</sub> on MAFLD by using a high-fat diet (HFD)-induced obese mouse model.</p><p><bold>Results:</bold> Treatment of mice with VC and VD<sub>3</sub> efficiently reversed the characteristics of MAFLD, such as obesity, dyslipidemia, insulin resistance, hepatic steatosis, and inflammation. VC and VD<sub>3</sub> showed similar beneficial effects as mentioned above in HFD-induced obese mice. Interestingly, VC and VD<sub>3</sub> 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.</p><p><bold>Conclusion:</bold> Together, the results indicate that the anti-MAFLD activities of VC and VD<sub>3</sub> are linked to improved gut-liver interactions <italic>via</italic> regulation of the gut microbiota and bile acid metabolism, and they may therefore prove useful in treating MAFLD clinically.</p>