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

Xiao-Lei Zhang; Lei Chen; Jiang Yang; Shan-Shan Zhao; Shi Jin; Na Ao; Jing Yang; Hui-Xin Liu; Jian Du

doi:10.3389/fmicb.2023.1117644

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

Front Microbiol. 2023 Feb 2:14:1117644. doi: 10.3389/fmicb.2023.1117644. eCollection 2023.

Authors

Xiao-Lei Zhang¹, Lei Chen^{2

3

4}, Jiang Yang¹, Shan-Shan Zhao^{2

3

4}, Shi Jin¹, Na Ao¹, Jing Yang^{2

3

4}, Hui-Xin Liu^{1

2

3

4}, Jian Du¹

Affiliations

¹ Department of Endocrinology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
² Institute of Health Sciences, China Medical University, Shenyang, Liaoning, China.
³ Institute of Life Sciences, China Medical University, Shenyang, Liaoning, China.
⁴ Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, China Medical University, Shenyang, Liaoning, China.

Abstract

Background: Non-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.

Methods: Rats 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.

Result: The 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.

Conclusion: VD 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.

Keywords: NAFLD; gut microbiota; sphingolipid metabolism; tyrosine metabolism; vitamin D.

Grants and funding

This research received financial support from the General Project of Liaoning Provincial Department of Education under Grant No. LJKZ0758.