{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:48:24Z","timestamp":1793324904966,"version":"4.5.0"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) are interrelated through insulin resistance (IR) and gut microbiota dysbiosis. This review evaluates the synergistic efficacy and mechanisms of a combined probiotic and metformin regimen in the management of PCOS, with a specific focus on the gut-ovary-metabolism axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature search was conducted following PROSPERO (ID: CRD420251143914) registration across PubMed, EMBASE, Web of Science, the China National Knowledge Infrastructure (CNKI), the Wanfang Database, and the VIP Database, prioritizing randomized controlled trials and retrospective studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The combination therapy suggests improved outcomes compared to metformin monotherapy, yielding significant improvements in metabolic, hormonal, and reproductive function. Crucially, probiotics alleviated metformin-induced gastrointestinal adverse effects, thereby enhancing treatment adherence. The proposed underlying mechanisms involve a synergistic restoration of gut microbial homeostasis, increased production of short-chain fatty acids, reinforcement of the intestinal barrier, and potentiated activation of the AMP-Activated Protein Kinase (AMPK) pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>As an adjunct supplement to metformin, probiotics represent a novel, evidence-supported therapeutic strategy for PCOS. This approach offers enhanced efficacy and tolerability, with potential implications for a broader spectrum of metabolic disorders including T2DM; however, given the current paucity of related studies, conclusions should be drawn cautiously.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      ], identifier [CRD420251143914].\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2025.1699600","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T15:22:21Z","timestamp":1768490541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Harnessing probiotic-metformin synergy: targeting the gut-microbiota metabolism axis to ameliorate polycystic ovary syndrome"],"prefix":"10.3389","volume":"12","author":[{"given":"Wanqiu","family":"Yang","sequence":"first","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yin","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingling","family":"Xie","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moyao","family":"Tan","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu","place":["Sichuan, 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