Eurotium cristatum ameliorates hyperuricemia-induced renal pyroptosis through microbiome-derived metabolome reprogramming

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.