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-inflammatory probiotics HF05 and HF06 synergistically alleviate ulcerative colitis and secondary liver injury.

Given the limited efficacy and adverse effects associated with conventional drugs, probiotics are emerging as a promising therapeutic strategy for mitigating the chronic nature of ulcerative colitis (UC) and its consequential secondary liver injury (SLI). Limosilactobacillus fermentum HF06 and Lactiplatibacillus plantarum HF05 are strains we screened with excellent anti-inflammatory and probiotic properties in vitro. In this study, the intervention of HF06 and HF05 in combination (MIXL) was found to be more effective in alleviating intestinal inflammation and secondary liver injury in UC mice compared to supplementing with the two strains individually. Results demonstrated that MIXL effectively attenuated colon shortening and weight loss, downregulated the expression of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 mRNA in the intestines, mitigated SLI, and augmented the enzymatic activities of SOD, CAT, and GSH-Px in the liver. MIXL enhances the intestinal barrier in UC mice, regulates the structure and composition of the gut microbiota, promotes the abundance of Lactobacillus, and suppresses the abundance of bacteria associated with inflammation and liver injury, including Clostridium_Sensu_Stricto_1, Escherichia, Shigella, Enterococcus, Corynebacterium, Desulfovibrio, and norank_f__Oscillospiraceae. This study demonstrated the synergistic effect of HF06 and HF05, providing a reliable foundation for the alleviation of UC.