American Chemical Society
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Folic Acid Protects against Hyperuricemia in C57BL/6J Mice via Ameliorating Gut–Kidney Axis Dysfunction

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journal contribution
posted on 2022-12-06, 20:15 authored by Peng Wang, Xiaoqi Zhang, Xian Zheng, Jingru Gao, Mengfei Shang, Jinghan Xu, Hui Liang
Emerging lines of research evidence point to a vital role of gut–kidney axis in the development of hyperuricemia (HUA), which has been identified as an increasing burden worldwide due to the high prevalence. The involved crosstalk which links the metabolic and immune-related pathways is mainly responsible for maintaining the axial homeostasis of uric acid (UA) metabolism. Nowadays, the urate-lowering drugs only aim to treat acute gouty arthritis as a result of their controversial clinical application in HUA. In this study, we established the HUA model of C57BL/6J mice to evaluate the effectiveness of folic acid on UA metabolism and further explored the underlying mechanisms. Folic acid attenuated the kidney tissue injury and excretion dysfunction, as well as the typical fibrosis in HUA mice. Molecular docking results also revealed the structure–activity relationship of the folic acid metabolic unit and the UA transporters GLUT9 and URAT1, implying the potential interaction. Also, folic acid alleviated HUA-induced Th17/Treg imbalance and intestinal tissue damage and inhibited the active state of the TLR4/NF-κB signaling pathway, which is closely associated with the circulating LPS level caused by the impaired intestinal permeability. Furthermore, the changes of intestinal microecology induced by HUA were restored by folic acid, including the alteration in the structure and species composition of the gut microbiome community, and metabolite short-chain fatty acids. Collectively, this study revealed that folic acid intervention exerted improving effects on HUA by ameliorating gut–kidney axis dysfunction.