{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:11Z","timestamp":1787029211634,"version":"build-2736575974"},"reference-count":102,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Joint Research Institute of Future Food and Great Health Industry, Guangxi University & Guangxi Zhongbo Nuocheng Biotechnology Co., Ltd.","award":["2025450001000763"],"award-info":[{"award-number":["2025450001000763"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Hyperuricemia, a common metabolic disorder characterized by elevated serum uric acid (UA) levels, can lead to severe complications such as gout and renal impairment. Conventional therapies, while effective, are frequently accompanied by significant adverse effects, underscoring the urgent need for safer therapeutic alternatives. Recent evidence identifies the intestine as a novel, pivotal regulator of UA homeostasis, presenting a promising therapeutic axis. This review delineates the intestinal mechanisms governing UA regulation and evaluates the therapeutic potential of natural active substances that target these pathways. We conducted a comprehensive review of recent preclinical studies focusing on intestinal mechanisms involved in UA metabolism, including the roles of gut microbiota, urate transport proteins, intestinal barrier function, and inflammation. Studies evaluating natural active substances\u2014such as polyphenols, polysaccharides, peptides, and plant extracts\u2014were systematically analyzed for their effects on gut-mediated UA regulation. Natural active substances have been shown to effectively alleviate hyperuricemia by modulating gut microbiota, enhancing UA intestinal excretion, reinforcing intestinal barrier function, and suppressing inflammatory pathways. Collectively, these findings demonstrate the multi-target efficacy of natural active substances within the intestines, offering a promising therapeutic strategy that warrants further investigation into nutrition-based intestinal interventions and novel pharmacological treatments for hyperuricemia.<\/jats:p>","DOI":"10.3390\/nu18060997","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:53:34Z","timestamp":1774274014000},"page":"997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intestinal Multi-Target Mechanisms of Natural Active Substances in Hyperuricemia Alleviation: Recent Progress"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1586-4699","authenticated-orcid":false,"given":"Ying","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Geriatric Nutrition and Health, Beijing Technology and Business University, Beijing 100080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziling","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Geriatric Nutrition and Health, Beijing Technology and Business University, Beijing 100080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Geriatric Nutrition and Health, Beijing Technology and Business University, Beijing 100080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Geriatric Nutrition and Health, Beijing Technology and Business University, Beijing 100080, China"},{"name":"Institute of Modern Fermentation Engineering and Future Foods, Guangxi University, Nanning 530004, China"},{"name":"Joint Research Institute of Future Foods and Comprehensive Health Industries, Guangxi University & Guangxi Zhongbo Nuocheng Biotechnology Co., Ltd., Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1560-8695","authenticated-orcid":false,"given":"Yousheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Modern Fermentation Engineering and Future Foods, Guangxi University, Nanning 530004, China"},{"name":"College of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103796","DOI":"10.1016\/j.numecd.2024.103796","article-title":"Hyperuricemia, A new cardiovascular risk","volume":"35","author":"Kuwabara","year":"2025","journal-title":"Nutr. 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