Combined Mitigation of Hyperuricemia by Co‐Cultured Monascus Purpureus M1 and Sanghuangporus Vaninii : Dual Modulation of Uric Acid Production, Excretion, and Gut Microbiota

Hyperuricemia (HUA) is a primary trigger for gout and poses a serious threat to human health. Metabolites from Monascus purpureus exhibit lipid-lowering and nephroprotective effects, while Sanghuangporus extracts have been proven to effectively reduce uric acid (UA) levels. However, the effects and underlying mechanisms of their co-culture (CMS) fermentation products remain unclear. This study examined the therapeutic effects and mechanisms of action of fermented products from Monascus purpureus M1 (MPF), Sanghuangporus vaninii (SVF), and their CMS in alleviating HUA. In vitro assays revealed MPF, SVF, and CMS substantially suppressed XOD activity. In vivo, they reduced UA levels in PO/HX-induced HUA mice, mitigated renal injury, and alleviated renal inflammation and oxidative stress. Mechanistically, these effects were associated with renal reabsorption transporters GLUT9/URAT1, upregulated secretory transporters OAT1/ABCG2, and increased intestinal UA transporters ABCG2 and GLUT9. Gut microbiota analysis revealed enrichment of Lactobacillus in the CMS group. Notably, CMS exhibited a more pronounced tendency toward efficacy compared with the individual fermentation products. Collectively, CMS fermentation of MPF and SVF shows potential as a natural strategy for the management of HUA through coordinated regulation of UA metabolism and gut microbiota. Practical Application: This study developed a novel fermentation strategy using the CMS of MPF and SVF. The metabolites derived from CMS demonstrated potential hypouricemic activity via multifaceted mechanisms-including modulation of xanthine oxidase (XOD) activity, regulation of urate transporters in the kidneys and intestines, and alteration of to the gut microbiota. This work not only provides a proof-of-concept for utilizing microbial CMS technology to develop novel functional foods but also opens a new avenue for converting edible and medicinal fungal resources into high-value health products.