School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China.
Engineering Research Center of Agricultural Microbiology Technology, Ministry of Education & Heilongjiang Provincial Key Laboratory of Ecological Restoration and Resource Utilization for Cold Region & Key Laboratory of Microbiology, College of Heilongjiang Province & School of Life Sciences, Heilongjiang University, Harbin 150080, China.
J Agric Food Chem. 2024 Feb 7;72(5):2573-2584. doi: 10.1021/acs.jafc.3c00984. Epub 2024 Jan 19.
Hyperuricemia (HUA) is a metabolic disorder characterized by an increase in the concentrations of uric acid (UA) in the bloodstream, intricately linked to the onset and progression of numerous chronic diseases. The tripeptide Pro-Glu-Trp (PEW) was identified as a xanthine oxidase (XOD) inhibitory peptide derived from whey protein, which was previously shown to mitigate HUA by suppressing UA synthesis and enhancing renal UA excretion. However, the effects of PEW on the intestinal UA excretion pathway remain unclear. This study investigated the impact of PEW on alleviating HUA in rats from the perspective of intestinal UA transport, gut microbiota, and intestinal barrier. The results indicated that PEW inhibited the XOD activity in the serum, jejunum, and ileum, ameliorated intestinal morphology changes and oxidative stress, and upregulated the expression of ABCG2 and GLUT9 in the small intestine. PEW reversed gut microbiota dysbiosis by decreasing the abundance of harmful bacteria (e.g., , , and ) and increasing the abundance of beneficial microbes (e.g., , , and ) and elevated the concentration of short-chain fatty acids. PEW upregulated the expression of occludin and ZO-1 and decreased serum IL-1β, IL-6, and TNF-α levels. Our findings suggested that PEW supplementation ameliorated HUA by enhancing intestinal UA excretion, modulating the gut microbiota, and restoring the intestinal barrier function.
高尿酸血症（HUA）是一种代谢紊乱，其特征是血液中尿酸（UA）浓度升高，与许多慢性疾病的发生和发展密切相关。三肽 Pro-Glu-Trp（PEW）是一种从乳清蛋白中分离出的黄嘌呤氧化酶（XOD）抑制肽，先前的研究表明，它通过抑制 UA 合成和增强肾脏 UA 排泄来减轻 HUA。然而，PEW 对肠道 UA 排泄途径的影响尚不清楚。本研究从肠道 UA 转运、肠道微生物群和肠道屏障的角度，探讨了 PEW 缓解大鼠 HUA 的作用。结果表明，PEW 抑制了血清、空肠和回肠中的 XOD 活性，改善了肠道形态变化和氧化应激，上调了小肠中 ABCG2 和 GLUT9 的表达。PEW 通过降低有害细菌（如 、 、 ）的丰度和增加有益微生物（如 、 、 ）的丰度以及提高短链脂肪酸的浓度来逆转肠道微生物群失调。PEW 上调了 occludin 和 ZO-1 的表达，并降低了血清 IL-1β、IL-6 和 TNF-α水平。我们的研究结果表明，PEW 通过增强肠道 UA 排泄、调节肠道微生物群和恢复肠道屏障功能来改善 HUA。
