Therapeutic effects of Isaria felina on postmenopausal osteoporosis: modulation of gut microbiota, metabolites, and immune responses

Background 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. Methods The effects of Isaria felina , derived from Cordyceps sinensis , on postmenopausal osteoporosis in rats are the focus of this study. Adult female Sprague-Dawley rats were categorized into control, postmenopausal osteoporosis (OVX), and Isaria felina -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. Results Micro-CT and histological assessments indicated significant improvements in bone loss and obesity control in OVX rats treated with Isaria felina . 16S rDNA sequencing revealed that Isaria felina corrected gut microbiota dysbiosis, particularly in the Bacteroides and Ruminococcus genera . Untargeted metabolomics highlighted alterations in nucleotide and lipid metabolism. Flow cytometry and ELISA analyses demonstrated that Isaria felina modulated the Th17/Treg immune balance, resulting in reduced levels of inflammatory cytokines IL-17 and TNF-α. Conclusions These findings indicate that Isaria felina mitigates bone loss in postmenopausal osteoporosis through modulation of gut microbiota and immune responses, underscoring its potential as a therapeutic agent for osteoporosis treatment.