Alteration of Gut Microbiome and Correlated Amino Acid Metabolism Contribute to Hyperuricemia and Th17-Driven Inflammation in Uox-KO Mice

Abstract

Although gut dysbiosis had been demonstrated to be an important factor affecting hyperuricemia (HUA) and gout, little is known for its potential mechanistic connections. In this study, Uox-KO mice model that with spontaneously developed pronounced HUA and urate nephropathy was used to explore the pathophysiologic mechanism of microbiota alterations in HUA and gout with integrated multi-omics analysis. 16S rRNA gene sequencing was performed to characterize the characteristic bacteria, and untargeted LC/MS analysis was applied to reveal the featured metabolites. Our results showed there was a significant shift in gut microbiota composition and function in Uox-KO mice compared to WT mice and apparent metabolomics differences between the two groups. Among them, amino acids metabolism appears to play a critical role. Correlation analysis further revealed that the characteristic metabolites were strongly influenced by the discrepant bacterial genera. Furthermore, impairment of intestinal integrity and profound alterations in the profile of solute carrier family resulted in dysregulation of amino acids transportation, which subsequently impacted serum uric acid level and CD4+ Th17 driven inflammation. Together, these data indicate that gut dysbiosis promotes purine metabolism disorder and inflammation in Uox-KO mice. Remodeling the gut microbiota is a promising strategy to combat HUA and gout.

The biomarkers discovery of hyperuricemia and gout: proteomics and metabolomics

“…Several studies have reported changes in the gut flora of people with hyperuricemia and found that some bacteria promote disease onset and progression ( Liu et al, 2020 ). In animal models of hyperuricemia and gout, specific metabolites have been linked to intestinal flora metabolism ( Wang et al, 2020b ; Song et al, 2022 ). A dysmetabolic intestinal flora may contribute to gout-related metabolism, thus promoting Th17 infiltration and further inflammatory symptoms.…”

Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout

“…Among them, amino acid metabolism plays a key role, and characteristic metabolites are strongly influenced by differential bacterial genera. Furthermore, an impaired gut integrity and profound alterations in the solute carrier family lead to dysregulated amino acid transport, which, in turn, affects the serum UA levels and CD4+ Th17-driven inflammation ( Song et al., 2022 ). Of course, research investigating the effect of gut microbiota on amino acid metabolism needs to be further conducted.…”

Vaginal homeostasis features of Vulvovaginal Candidiasis through vaginal metabolic profiling

“…Metabolomics studies can investigate a variety of biological processes and phenotypes by means of metabolites [36], such as amino acid and lipid metabolites [37]. Metabolomics has been extensively studied in inflammation-related diseases such as hyperuricemia [38], inflammatory bowel disease [39], rheumatoid arthritis [40], sepsis [41], liver failure [42], and endometriosis [43]. Research evaluating cervical and vaginal lavage fluids in patients with inflammatory vaginal disease has found associations between the composition of vaginal microflora and metabolite profiles [32].…”