Gut microbiota, microbial metabolites, and microbiome-directed nutritional interventions in hyperuricemia and gout:...

Hyperuricemia (HUA) and gout are increasingly prevalent metabolic disorders, imposing a substantial global health burden. Although conventional urate-lowering therapies remain the clinical cornerstone, their long-term effectiveness is frequently constrained by adverse effects, variable patient responses, and limited capacity to address underlying metabolic and inflammatory disturbances. Emerging evidence highlights the gut microbiota and its interactions with host metabolic pathways as important modulators of systemic urate homeostasis, positioning microbiome-directed nutritional strategies as promising approaches for hyperuricemia management. This review synthesizes the microbiota-mediated regulation of HUA and gout. Although the majority of current evidence remains preclinical, keystone microbial taxa, particularly specific strains within the Bifidobacterium genus and the updated Lactobacillaceae family, contribute to urate homeostasis through three interconnected mechanisms: (i) enzymatic interception of dietary purines; (ii) reprogramming of host urate transport pathways to favor urate excretion while limiting reabsorption; and (iii) reinforcement of intestinal barrier integrity and attenuation of systemic inflammation via short-chain fatty acid- and tryptophan-derived immunometabolic pathways. Emerging microbiome-directed strategies, including dietary modulation, functional probiotics, food-grade engineered probiotics, and fecal microbiota transplantation, show promising potential as investigational strategies for restoring urate homeostasis. Furthermore, we evaluate the translational landscape of microbiome-based interventions, highlighting advances in synthetic biology and microbiome-assisted complementary strategies alongside conventional therapies. Addressing major challenges - including strain-specific functional heterogeneity, colonization durability, and host variability - will be critical. Ultimately, integrating strain-resolved multiomics, causal inference frameworks, and artificial intelligence-assisted modeling represents a key research priority to guide the future development of next-generation precision microbiome interventions for HUA and gout. © 2026 Society of Chemical Industry.