Whey Protein Peptide Pro-Glu-Trp Ameliorates Hyperuricemia by Enhancing Intestinal Uric Acid Excretion, Modulating the Gut Microbiota, and Protecting the Intestinal Barrier in Rats.

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., Bacteroides, Alloprevotella, and Desulfovibrio) and increasing the abundance of beneficial microbes (e.g., Muribaculaceae, Lactobacillus, and Ruminococcus) and elevated the concentration of short-chain fatty acids. PEW upregulated the expression of occludin and ZO-1 and decreased serum IL-1ß, 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.

Anti-hyperuricemic and nephroprotective effects of whey protein hydrolysate in potassium oxonate induced hyperuricemic rats.

BACKGROUND: Hyperuricemia (HUA) is a serious public health concern globally that needs to be solved. It is closely related to gout and other metabolic diseases. To develop a safe and effective dietary supplementation for alleviating HUA, we investigated the effects of whey protein hydrolysate (WPH) on HUA and associated renal dysfunction and explored their underlying mechanism. RESULTS: Potassium oxonate was used to induce HUA in model rats, who were then administered WPH for 21 days. The results showed that WPH significantly inhibited xanthine oxidase and adenosine deaminase activity in serum and liver, decreased uric acid (UA), creatinine, and blood urea nitrogen levels in serum, and increased the UA excretion in urine. In addition, WPH downregulated the expression of urate transporter 1 and upregulated the expression of organic anion transporter 1, adenosine triphosphate binding cassette subfamily G member 2, organic cation/carnitine transporters 1 and 2, and organic cation transporter 1 in kidneys. CONCLUSION: These findings demonstrated for the first time that WPH could alleviate HUA by inhibiting UA production and promoting UA excretion, and improve the renal dysfunction caused by HUA. Thus, WPH may be a potential functional ingredient for the prevention and treatment of HUA and associated renal dysfunction. © 2021 Society of Chemical Industry.