Shan Baixi, Wu Mingyu, Chen Ting, Tang Weiwei, Li Ping, Chen Jun
State Key Laboratory of Natural Medicines, China Pharmaceutical University Nanjing 210009, P. R. China.
Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University Nanjing 210009, P. R. China.
Am J Chin Med. 2022;50(8):2199-2221. doi: 10.1142/S0192415X22500951. Epub 2022 Oct 20.
Hyperuricemia (HUA) and its associated metabolic diseases seriously threaten human health, and commensal microbiota has been identified as one of the environmental triggers of HUA. The role of berberine (BBR) in the treatment of HUA has begun to receive attention in recent years. However, how BBR modulates the microbiota to slow HUA progression is unclear. In this study, we showed that BBR alleviated potassium oxonate (PO)-induced HUA in mice by suppressing the expression of xanthine oxidase (XOD) in the liver and urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in the kidney. The BBR also improved renal inflammation by inhibiting the expression of TNF-[Formula: see text], IL-1[Formula: see text], and caspase-1. Subsequently, we evaluated whether the observed anti-HUA effects of BBR were associated with changes in gut microbial structure in mice. 16S rRNA sequencing data showed that BBR significantly altered the community compositional structure of the gut microbiota. Specifically, BBR enriched the abundance of , , , and . Antibiotic treatment can reverse the anti-HUA effects of BBR that further supports the role of the gut microbiota. In conclusion, our study provides evidence that BBR ameliorates PO-induced HUA by modulating the gut microbiota.
高尿酸血症（HUA）及其相关的代谢性疾病严重威胁人类健康，共生微生物群已被确定为HUA的环境触发因素之一。近年来，黄连素（BBR）在治疗HUA中的作用开始受到关注。然而，BBR如何调节微生物群以减缓HUA进展尚不清楚。在本研究中，我们发现BBR通过抑制肝脏中的黄嘌呤氧化酶（XOD）以及肾脏中的尿酸转运蛋白1（URAT1）和葡萄糖转运蛋白9（GLUT9）的表达，减轻了氧嗪酸钾（PO）诱导的小鼠高尿酸血症。BBR还通过抑制TNF-α、IL-1β和半胱天冬酶-1的表达改善了肾脏炎症。随后，我们评估了观察到的BBR抗HUA作用是否与小鼠肠道微生物结构的变化有关。16S rRNA测序数据表明，BBR显著改变了肠道微生物群的群落组成结构。具体而言，BBR增加了[具体菌属1]、[具体菌属2]、[具体菌属3]和[具体菌属4]的丰度。抗生素治疗可逆转BBR的抗HUA作用，这进一步支持了肠道微生物群的作用。总之，我们的研究提供了证据，证明BBR通过调节肠道微生物群改善PO诱导的HUA。
