College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China.
Institute of Vegetable, Gansu Academy of Agricultural Sciences, Lanzhou 730070, China.
Pharmacol Res. 2022 Aug;182:106350. doi: 10.1016/j.phrs.2022.106350. Epub 2022 Jul 14.
Hyperuricemia is a critical threat to human health, and conventional medical treatment only aims to treat acute gouty arthritis. Purine diet-mediated chronic hyperuricemia and related syndromes are neglected in clinical therapeutics. In this study, the prevention ability of Lacticaseibacillus rhamnosus Fmb14, screened from Chinese yogurt, was evaluated in chronic purine-induced hyperuricemia (CPH) mice. After 12 weeks of Fmb14 administration, serum uric acid (SUA) in CPH mice decreased by 36.8 %, from 179.1 to 113.2 µmol/L, and the mortality rate decreased from 30 % to 10 %. The prevention role of Fmb14 in CPH was further investigated, and the reduction of uric acid by Fmb14 was attributed to the reduction of XOD (xanthine oxidase) in the liver and URAT1 in the kidney, as well the promotion of ABCG2 in the colon. Fmb14 administration Increased ZO-1 and Occludin expression in the colon and decreased fibrosis degree in the kidney indicated that Fmb14 administration had preventive effects through the gut-kidney axis in CPH. In specific, Fmb14 administration upregulated the diversity of gut microbiota, increased short-chain fatty acids (SCFA) by 35 % in colon materials and alleviated the inflammatory response by reducing biomarkers levels of IL-1β, IL-18 and TNF-α at 11.6 %, 21.7 % and 26.5 % in serum, compared to CPH group, respectively. Additionally, 16 S rRNA sequencing showed 31.5 % upregulation of Prevotella, 20.5 % and 21.6 % downregulation of Ruminococcus and Suterella at the genus level, which may be a new gut microbial marker in hyperuricemia. In conclusion, Fmb14 ameliorated CPH through the gut-kidney axis, suggesting a new strategy to prevent hyperuricemia.
高尿酸血症是对人类健康的严重威胁，传统医学治疗仅针对急性痛风性关节炎。嘌呤饮食介导的慢性高尿酸血症和相关综合征在临床治疗中被忽视。本研究评估了从中国酸奶中筛选出的鼠李糖乳杆菌 Fmb14 对慢性嘌呤诱导高尿酸血症（CPH）小鼠的预防能力。Fmb14 给药 12 周后，CPH 小鼠血清尿酸（SUA）降低 36.8%，从 179.1µmol/L 降至 113.2µmol/L，死亡率从 30%降至 10%。进一步研究了 Fmb14 在 CPH 中的预防作用，Fmb14 降低尿酸的作用归因于肝脏黄嘌呤氧化酶（XOD）和肾脏尿酸盐转运体 1（URAT1）的减少以及结肠 ABCG2 的促进。Fmb14 给药增加了结肠中 ZO-1 和 Occludin 的表达，并降低了肾脏纤维化程度，表明 Fmb14 通过 CPH 中的肠-肾轴发挥预防作用。具体而言，Fmb14 给药增加了肠道微生物群的多样性，使结肠组织中的短链脂肪酸（SCFA）增加了 35%，并通过降低血清中 IL-1β、IL-18 和 TNF-α 的生物标志物水平分别降低了 11.6%、21.7%和 26.5%，从而减轻了炎症反应。此外，16S rRNA 测序显示普雷沃氏菌上调 31.5%，瘤胃球菌和 Suterella 下调 20.5%和 21.6%，这可能是高尿酸血症的新肠道微生物标志物。总之，Fmb14 通过肠-肾轴改善了 CPH，为预防高尿酸血症提供了新策略。
