National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Chinese Center of Disease Control and Prevention, Beijing, China.
School of Medicine, Nankai University, Tianjin, China.
Food Funct. 2024 Jun 4;15(11):6015-6027. doi: 10.1039/d4fo00118d.
Hyperuricemia (HUA) is a widespread metabolic disorder. Probiotics have drawn increasing attention as an adjunctive treatment with fewer side effects. However, thus far the effective strains are limited and the mechanisms for their serum uric acid (SUA)-lowering effect are not well understood. Along this line, we conducted the current study using a hyperuricemia mouse model induced by potassium oxonate and adenine. A novel strain of named D2022 was identified to have significant SUA-lowering capability. D2022 significantly reduced SUA levels by inhibiting uric acid synthesis and regulating uric acid transportation. It was also found that D2022 alleviated HUA-induced renal inflammatory injury involving multiple signaling pathways. By focusing on the expression of NLRP3-related inflammatory genes, we found correlations between the expression levels of these genes and free fatty acid receptors (FFARs). In addition, oral administration of D2022 increased short-chain fatty acids (SCFAs) in cecal samples, which may be one of the mechanisms by which oral probiotics alleviate renal inflammation. Serum untargeted metabolomics showed changes in a variety of serum metabolites associated with purine metabolism and inflammation after oral administration of D2022, further confirming its systemic bioactivity. Finally, it was proved that D2022 improved intestinal barrier function. In conclusion, D2022 can alleviate HUA and HUA-induced nephropathy by increasing the production of SCFAs in the gut and systemic metabolism.
高尿酸血症（HUA）是一种广泛存在的代谢紊乱。益生菌作为一种副作用较少的辅助治疗方法，引起了越来越多的关注。然而，迄今为止，有效的菌株有限，其降低血清尿酸（SUA）的作用机制尚不清楚。沿着这条线，我们使用氧嗪酸钾和腺嘌呤诱导的高尿酸血症小鼠模型进行了当前的研究。鉴定出一种名为 D2022 的新型菌株，具有显著的降低 SUA 的能力。D2022 通过抑制尿酸合成和调节尿酸转运来显著降低 SUA 水平。还发现 D2022 减轻了 HUA 诱导的肾炎症损伤，涉及多个信号通路。通过关注 NLRP3 相关炎症基因的表达，我们发现这些基因的表达水平与游离脂肪酸受体（FFARs）之间存在相关性。此外，D2022 的口服给药增加了盲肠样本中的短链脂肪酸（SCFAs），这可能是口服益生菌减轻肾炎症的机制之一。血清非靶向代谢组学显示，口服 D2022 后与嘌呤代谢和炎症相关的各种血清代谢物发生变化，进一步证实了其系统生物活性。最后，证明 D2022 改善了肠道屏障功能。总之，D2022 通过增加肠道和全身代谢中 SCFAs 的产生来缓解 HUA 和 HUA 诱导的肾病。
