Zhou Shuxin, Wen Xin, Lessing Duncan James, Chu Weihua
Department of Microbiology and Synthetic Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China.
Probiotics Antimicrob Proteins. 2025 Apr 9. doi: 10.1007/s12602-025-10532-3.
Hyperuricemia, characterized by elevated levels of uric acid in the blood, poses a significant health threat due to its association with various adverse health outcomes, and lactic acid bacteria from the gut microbiota may offer solutions. Our investigation focused on Lacticaseibacillus paracasei CPU202306, isolated from fermented pickles for its potent uric acid degradation and probiotic properties. This bacterium effectively reduced blood uric acid levels by breaking down uric acid and inhibiting hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) enzymes. Additionally, it stimulated the production of short-chain fatty acid (SCFAs) in the colon, enhancing the expression of uric acid secretion transport proteins (ATP-binding cassette sub-family G member 2 and organic anion transporter 3) while suppressing absorption transport proteins (glucose transporter 9 and uric acid transporter 1). This orchestrated process promoted uric acid excretion. L. paracasei CPU202306 also improved gut microbiota health by reinforcing tight junction proteins, shifting the microbiota to a healthier composition, and reducing harmful bacteria. This transformation inhibited kidney TLR4/MyD88/NF-κB inflammatory signaling, leading to a significant decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines, mitigating kidney inflammation. Furthermore, the bacterium supported kidney health by influencing amino acid metabolic pathways linked to the gut-kidney axis. In summary, our study highlights the diverse mechanisms through which L. paracasei CPU202306 addresses hyperuricemia, showcasing its therapeutic potential for this condition.
高尿酸血症的特征是血液中尿酸水平升高，由于其与各种不良健康后果相关联，对健康构成重大威胁，而来自肠道微生物群的乳酸菌可能提供解决方案。我们的研究重点是副干酪乳杆菌CPU202306，它是从发酵泡菜中分离出来的，具有强大的尿酸降解能力和益生菌特性。这种细菌通过分解尿酸以及抑制肝脏中的黄嘌呤氧化酶（XOD）和腺苷脱氨酶（ADA），有效降低了血液中的尿酸水平。此外，它还刺激了结肠中短链脂肪酸（SCFA）的产生，增强了尿酸分泌转运蛋白（ATP结合盒亚家族G成员2和有机阴离子转运蛋白3）的表达，同时抑制了吸收转运蛋白（葡萄糖转运蛋白9和尿酸转运蛋白1）。这一精心编排的过程促进了尿酸的排泄。副干酪乳杆菌CPU202306还通过加强紧密连接蛋白、使微生物群组成向更健康的方向转变以及减少有害细菌，改善了肠道微生物群的健康状况。这种转变抑制了肾脏TLR4/MyD88/NF-κB炎症信号通路，导致促炎细胞因子显著减少，抗炎细胞因子增加，减轻了肾脏炎症。此外，这种细菌通过影响与肠-肾轴相关的氨基酸代谢途径来维护肾脏健康。总之，我们的研究突出了副干酪乳杆菌CPU202306解决高尿酸血症的多种机制，展示了其对这种病症的治疗潜力。
