Project description:Fermented foods harbor beneficial microbes that support gut health and metabolic balance, offering natural probiotic strategies for managing conditions such as hyperuricemia through modulation of the gut microbiota and their derived metabolites. We demonstrate that Eurotium cristatum (E. cris), a dominant probiotic fungus in Fu brick tea, can directly utilize uric acid (UA) as a carbon source and ameliorate hyperuricemia progression by reprogramming the gut microbiome and metabolome, thereby alleviating NLRP3-mediated inflammation and pyroptosis in renal tissues. Oral administration of E. cristatum in hyperuricemic mice upregulated the expression of ATP-binding cassette subfamily G member 2 (ABCG2) in both the kidney and intestine, as well as the intestinal tight junction protein ZO-1, suggesting enhanced UA excretion and maintenance intestinal permeability. Microbiota analysis revealed that E. cristatum reversed dysbiosis by enriching beneficial bacteria (Coprococcus, Ruminococcus) while reducing pathogenic taxa (Turicibacteraceae, Clostridiaceae). Correlation analyses further indicated that these changes were linked to the restoration of the host's co-metabolite profile, characterized by enhanced purine degradation (decreased xanthine/hypoxanthine) and control amino acid metabolism (regulation of the urea cycle, histidine metabolism and the branched-chain amino acid pathway), which synergistically promoted UA clearance and reduced systemic metabolic burden. Notably, fecal microbiota transplantation in the intervention group replicated these effects, confirming that these benefits depend on the remodeling of the microbiota. Furthermore, we confirmed that the microbiome remodeling induced by E. cristatum improved the urea cycle, histidine metabolism and contributed to the suppression of renal macrophage infiltration and NLRP3/GSDMD-mediated pyroptosis. In summary, this study elucidates how a food-derived probiotic fungus reshapes the gut microbiota and its metabolome to provide renal protection by promoting UA catabolism, the urea cycle and histidine metabolism, thereby offering new perspectives for probiotic intervention strategies.

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Expressional profile of liver of CGMCC No.8730 Eurotium cristatum fermented dark tea fed high-fat diet rats

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