{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T10:26:36Z","timestamp":1777890396476,"version":"3.51.4"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To clarify the molecular mechanisms through which lobetyolin (LT) modifies the gut microbiota-bile acid axis to multitarget the regulation of hyperandrogenism, insulin resistance, chronic low-grade inflammation, and endometrial dysfunction, consequently breaking the vicious cycle and improving the pathological phenotype of polycystic ovary syndrome (PCOS), thereby establishing a theoretical basis and experimental validation for the advancement of LT as a systemic therapeutic agent for PCOS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A DHEA-induced PCOS murine model was administered LT (i.p. for 28 days). We monitored hormone levels in the serum, glucose tolerance, and estrus cycle. Ovarian steroidogenic enzyme expression (CYP11A1, CYP17A1, and CYP19A1) was assessed by qPCR, while inflammatory markers (IL-6, TNF-\u03b1, TLR4, and NF-\u03baB) were quantified by ELISA.16S rRNA sequencing was performed for gut microbiota and focused bile acid metabolomics. Uterine molecular markers were evaluated through vascular endothelial growth factor A (VEGFA)\/vascular endothelial growth factor receptor (VEGFR2), tissue inhibitor of metalloproteinases 1(TIMP1\/2), and matrix metalloproteinase 2\/9 (MMP2\/9).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main results<\/jats:title>\n                    <jats:p>\n                      LT restored estrous cyclicity, lowered the LH\/FSH ratio and serum testosterone levels, and improved insulin sensitivity. Androgen Network Modulation: LT decreased CYP11A1\/CYP17A1 and elevated CYP19A1, showing \u201cupstream inhibition-downstream activation.\u201d LT also boosted \u03b1-diversity, adjusted the F\/B ratio, enriched\n                      <jats:italic>Dubosiella<\/jats:italic>\n                      \/\n                      <jats:italic>Muribaculum<\/jats:italic>\n                      , and inhibited\n                      <jats:italic>Lachnospiraceae and Alistipes<\/jats:italic>\n                      . Higher HCA and TCDCA levels are associated with improved metabolism. LT alleviated pathological vascular remodeling in the uterus by downregulating VEGFA\/VEGFR2 and MMP2\/9, and by overexpressing TIMP1\/2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LT modulates the microbiota-bile acid axis to coordinately ameliorate hyperandrogenism, insulin resistance, chronic inflammation, and uterine dysfunction. This intervention blocks the pathological cascade of PCOS. The findings provide a subsequent mechanistic studies on PCOS prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1810261","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:36:49Z","timestamp":1777613809000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lobetyolin reshapes gut microbiota and bile acid metabolism to improve androgen-driven PCOS phenotypes in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Lijuan","family":"Li","sequence":"first","affiliation":[{"name":"Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, Changzhi Medical College, Changzhi","place":["Shanxi, China"]},{"name":"School of Nursing, Changzhi Medical College, Changzhi","place":["Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pingping","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Nursing, Changzhi Medical College, Changzhi","place":["Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Nursing, Changzhi Medical College, Changzhi","place":["Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, Changzhi Medical College, Changzhi","place":["Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Nursing, Changzhi Medical College, Changzhi","place":["Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingtao","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Nursing, Changzhi Medical College, Changzhi","place":["Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruyu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Nursing, Changzhi Medical College, Changzhi","place":["Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guofeng","family":"Duan","sequence":"additional","affiliation":[{"name":"Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, Changzhi Medical College, Changzhi","place":["Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aixiang","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Nursing, Changzhi Medical College, Changzhi","place":["Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100507","DOI":"10.1016\/j.impact.2024.100507","article-title":"Evaluating the potential of daily intake of polystyrene microplastics via drinking water in inducing PCOS and its ovarian fibrosis progression using female zebrafish","volume":"34","author":"Adhikari","year":"2024","journal-title":"NanoImpact"},{"key":"B2","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1080\/09513590600906607","article-title":"Vascular endothelial growth factor and basic fibroblast growth factor in polycystic ovary syndrome during controlled ovarian hyperstimulation","volume":"22","author":"Artini","year":"2006","journal-title":"Gynecol. 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