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Normally, approximately two\u2010thirds of urate elimination is renal. However, chronic kidney disease (CKD) and other causes of decreased renal urate elimination drive hyperuricemia in most with gout. This places more demand on elimination of urate via the gut, where diet, purine metabolism, and microbiota intersect. Heritable impairment of urate transport into the gut is common and promotes hyperuricemia, renal urate overload, and early\u2010onset and palpable tophaceous gout phenotypes. <jats:italic>Lactobacilli<\/jats:italic>, by sequestering and modifying ambient purines, are being studied for the potential to suppress diet\u2010induced urate generation and associated gout flares. Landmark preclinical studies recently revealed much higher\u2010capacity urate\u2010lowering effects of diverse, obligate, and facultative anaerobic human and mouse gut microbiota (predominantly of the Bacillota phylum) termed purine\u2010degrading bacteria (PDB). A conserved gene cluster in PDB drives urate conversion to lactate or anti\u2010inflammatory short\u2010chain fatty acids. When mice are rendered deficient in hepatic uricase to mimic human uricase absence, microbiota depletion rapidly elevates both cecal and serum urate, which is reversible by PDB administration. In healthy human volunteers with normal renal function, antibiotic\u2010induced gut microbiota depletion decreases the urate\u2010lowering gene cluster unique to PDB and elevates fecal urate. Also, prior exposure to antibiotics with anaerobic coverage has been linked to heightened incident gout risk. Notably, intestinal dysbiosis that includes Bacillota depletion has been observed in gout cohorts. Therefore, the capacity of diverse gut bacterial strains to biochemically compensate for human limits in urate disposition suggests novel probiotic treatment approaches for gout with inadequate pharmacologic control of both flares and hyperuricemia. This is particularly so for severe CKD, which limits the options and maximal doses for use of conventional oral urate\u2010lowering drugs.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art43118-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1002\/art.43118","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T02:19:08Z","timestamp":1737339548000},"page":"955-965","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["The Gut Microbiome in Hyperuricemia and 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