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

Background: Previous studies have demonstrated that both vitamin C (VC) and vitamin D 3 (VD 3) 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 VD 3 on MAFLD by using a high-fat diet (HFD)-induced obese mouse model. Results: Treatment of mice with VC and VD 3 efficiently reversed the characteristics of MAFLD, such as obesity, dyslipidemia, insulin resistance, hepatic steatosis, and inflammation. VC and VD 3 showed similar beneficial effects as mentioned above in HFD-induced obese mice. Interestingly, VC and VD 3 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 VD 3 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.