{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T13:26:00Z","timestamp":1794317160431,"version":"4.9.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The intricate relationship between human health and gut microecology has emerged as a central theme in contemporary medical research. Postmenopausal osteoporosis, primarily driven by estrogen deficiency, remains a major health concern. Traditional Chinese herbal medicines have attracted significant interest for their promising role in osteoporosis treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effects of <jats:italic>Isaria felina<\/jats:italic>, derived from <jats:italic>Cordyceps sinensis<\/jats:italic>, on postmenopausal osteoporosis in rats are the focus of this study. Adult female Sprague-Dawley rats were categorized into control, postmenopausal osteoporosis (OVX), and <jats:italic>Isaria felina<\/jats:italic>-treated (IF+OVX) groups. Following a 12-week treatment period, various analyses, including micro-CT, histological assessments, 16S rDNA sequencing, untargeted metabolomics, flow cytometry, and ELISA, were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Micro-CT and histological assessments indicated significant improvements in bone loss and obesity control in OVX rats treated with <jats:italic>Isaria felina<\/jats:italic>. 16S rDNA sequencing revealed that <jats:italic>Isaria felina<\/jats:italic> corrected gut microbiota dysbiosis, particularly in the <jats:italic>Bacteroides<\/jats:italic> and <jats:italic>Ruminococcus genera<\/jats:italic>. Untargeted metabolomics highlighted alterations in nucleotide and lipid metabolism. Flow cytometry and ELISA analyses demonstrated that <jats:italic>Isaria felina<\/jats:italic> modulated the Th17\/Treg immune balance, resulting in reduced levels of inflammatory cytokines IL-17 and TNF-\u03b1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings indicate that <jats:italic>Isaria felina<\/jats:italic> mitigates bone loss in postmenopausal osteoporosis through modulation of gut microbiota and immune responses, underscoring its potential as a therapeutic agent for osteoporosis treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1508634","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T08:40:50Z","timestamp":1744188050000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Therapeutic effects of Isaria felina on postmenopausal osteoporosis: modulation of gut microbiota, metabolites, and immune 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