Vitamin D alleviates non-alcoholic fatty liver disease via restoring gut microbiota and metabolism

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. Dysbiosis of gut microbiome has been identified as one of the key environmental factors contributing to NAFLD. As an essential nutrition, Vitamin D (VD) plays an important role in regulating gut microbiota based on its receptor (Vitamin D Receptor, VDR) which is highly expressed in the gastrointestinal tract.MethodsRats were fed with HFD (high-fat diet) for 12 weeks. And the rats were treated with VD two times a week by intraperitoneal injection for 12 weeks. H&E staining combined with plasma biochemical index was performed to characterize pathological changes and function of the liver. Fecal microbiota 16S rRNA gene sequencing and metabolomics were taken to reveal the altered gut microbiota and metabolites.ResultThe VD alleviates the HFD-induced lipid accumulation in the liver as well as decreases the levels of amlodipine besylate (ALT) and amlodipine aspartate (AST). VD supplement decreased the ratio of phylum Firmicutes/Bacteroidetes (F/B) but increased alpha diversity. In addition, the VD treatment improved the HFD-induced gut microbiota by increasing the Prevotella and Porphyromonadaceae and decreasing Mucispirillum, Acetatifactor, Desulfovibrio, and Oscillospira abundance. Furthermore, the capability of tyrosine metabolism, tryptophan metabolism, arginine biosynthesis, and sphingolipid metabolism was enhanced after VD treatment. Consistently, Prevotella positively correlated with tryptophan metabolism and sphingolipid metabolism. Importantly, the Prevotella abundance was positively associated with serotonin, melatonin, tryptamine, L-arginine, and 3-dehydrosphinganine which synthesize from tryptophan, tyrosine, arginosuccinate, and serine, respectively.ConclusionVD treatment inhibited HFD-induced NAFLD accompany by dysbiosis gut microbiota and metabolites, suggesting that VD supplement could be a potential intervention used for NAFLD treatment by targeting the specific microbiota.

Gut microbiota in the association between obesity and kidney function decline: a metagenomics-based study in a rat model

“…The role of diet is vital in the development of obesity, diabetes, and allergies, and a HFD is frequently employed to induce obesity in animal models [ 15 , 25 , 26 ]. After a 20-week intervention with a HFD, we observed that rats became obese and experienced a notable increase in both lipid and blood glucose levels, in agreement with previous studies [ 27 ]. Additionally, rats in the HFD group exhibited increased levels of creatinine and urea nitrogen in their peripheral blood.…”

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

“…Recent studies have shown that VDR improves aging-related MAFLD by positively regulating mitochondrial function [202]. Additionally, the improvement of gut microbes is considered to be another potential mechanism by which vitamin D alleviates highfat diet-induced MAFLD [203]. Overall, the mechanism by which vitamin D works is inextricably linked to other metabolic pathways, and understanding the physiopathology of vitamin D will help unravel the mystery of MAFLD.…”

Exploring the interactions between metabolic dysfunction-associated fatty liver disease and micronutrients: from molecular mechanisms to clinical applications

“…Phototherapy-enhanced active vitamin D3 in mice mitigates hepatocyte apoptosis, inflammation, fibrosis, and insulin/leptin resistance caused by a CDAA diet ( 76 ). Additionally, vitamin D treatment curbs MAFLD induced by a high-fat diet (HFD), involving gut microbiota ( 77 ) and metabolic regulation ( 78 ), and modulates lipid metabolism through the PPARa signaling pathway ( 79 ). Vitamin D-regulated miRNAs are implicated in MAFLD pathogenesis, though more research is needed ( 80 ).…”