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

作者：Qingling Chen, Lili Zhao, Ling Mei, Xiaotong Zhao, Ping Han, Jie Liu, Chao Meng, Ruifang Li, Rui Zhong, Kai Wang, Jia Li · 发表于：Frontiers in Pharmacology · 年份：2023 · DOI：10.3389/fphar.2023.1163694 · 被引用次数：26 · 研究领域：Liver Disease Diagnosis and Treatment、Diet and metabolism studies、Gut microbiota and health

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...