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Although conventional urate\u2010lowering therapies remain the clinical cornerstone, their long\u2010term 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\u2010directed nutritional strategies as promising approaches for hyperuricemia management. This review synthesizes the microbiota\u2010mediated regulation of HUA and gout. Although the majority of current evidence remains preclinical, keystone microbial taxa, particularly specific strains within the\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    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\u2010chain fatty acid\u2010 and tryptophan\u2010derived immunometabolic pathways. Emerging microbiome\u2010directed strategies, including dietary modulation, functional probiotics, food\u2010grade engineered probiotics, and fecal microbiota transplantation, show promising potential as investigational strategies for restoring urate homeostasis. Furthermore, we evaluate the translational landscape of microbiome\u2010based interventions, highlighting advances in synthetic biology and microbiome\u2010assisted complementary strategies alongside conventional therapies. Addressing major challenges \u2013 including strain\u2010specific functional heterogeneity, colonization durability, and host variability \u2013 will be critical. Ultimately, integrating strain\u2010resolved multiomics, causal inference frameworks, and artificial intelligence\u2010assisted modeling represents a key research priority to guide the future development of next\u2010generation precision microbiome interventions for HUA and gout. \u00a9 2026 Society of Chemical Industry.\n                  <\/jats:p>","DOI":"10.1002\/jsfa.71016","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:10:48Z","timestamp":1787731848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut microbiota, microbial metabolites, and microbiome\u2010directed nutritional interventions in hyperuricemia and gout: mechanisms and translational opportunities"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7129-2704","authenticated-orcid":false,"given":"Xiangfeng","family":"Zheng","sequence":"first","affiliation":[{"name":"College of Food 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