Bacteroides fragilis-derived succinic acid promotes the degradation of uric acid by inhibiting hepatic AMPD2: Insight into how plant-based berberine ameliorates hyperuricemia

作者：Li‐Bin Pan, Ru Feng, Jiachun Hu, Hang Yu, Qian Tong, Xinyu Yang, Jian‐Ye Song, Hui Xu, Mengliang Ye, Zhengwei Zhang, Jie Fu, Haojian Zhang, Jin‐Yue Lu, Zhao Zhai, Jingyue Wang, Yi Zhao, Hengtong Zuo, Hui Xiang, Jian‐Dong Jiang, Yan Wang · 发表于：Acta Pharmaceutica Sinica B · 年份：2025 · DOI：10.1016/j.apsb.2025.08.009 · 被引用次数：6 · 研究领域：Berberine and alkaloids research、Ginseng Biological Effects and Applications、Gout, Hyperuricemia, Uric Acid

, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.