Comprehensive profiling of gut microbiota in postmenopausal osteoporosis

Background/aim: Osteoporosis is a multifactorial skeletal disease that predominantly affects postmenopausal women and is characterized by reduced bone mass and an increased risk of fractures. Growing evidence suggests that the gut microbiota plays a pivotal role in bone metabolism through immunological, endocrine, and metabolic pathways, forming the basis of the so-called gut– bone axis. This study aimed to characterize gut microbiota composition in postmenopausal women with osteoporosis compared with healthy controls. Materials and methods: Forty postmenopausal women aged 55–65 years were classified into osteoporosis (n = 20) and healthy control (n = 20) groups based on dual-energy X-ray absorptiometry T-scores. Fecal samples were collected, and gut microbiota composition was evaluated with full-length 16S rRNA gene sequencing using Oxford Nanopore Technologies. Results: No significant differences were observed in clinical or demographic characteristics between groups, except for the expected lower bone mineral density (BMD) in the osteoporosis group. Alpha-diversity indices showed no statistically significant differences, although a trend toward reduced microbial richness was observed in the osteoporotic participants. Beta-diversity analysis revealed a modest but significant phylogenetic distinction via weighted UniFrac analysis (p < 0.05). Short-chain fatty acid-producing species, including Faecalibacterium prausnitzii, Anaerostipes faecalis, and Lactonifactor longoviformis, were significantly reduced in the osteoporosis group. F. prausnitzii abundance was positively correlated with the femoral neck T-score (r = 0.41, p = 0.018), whereas Oxobacter pfennigii showed a negative correlation with lumbar spine BMD (r = –0.43, p = 0.015). Conclusion: Postmenopausal osteoporosis is associated with a distinct gut microbiota profile marked by reduced antiinflammatory and estrogen-modulating taxa alongside increased proinflammatory species. These alterations may contribute to impaired bone metabolism through disrupted calcium absorption, systemic inflammation, and hormonal dysregulation. These findings further support the gut– bone axis and highlight the potential of gut microbiota as a biomarker and therapeutic target in osteoporosis.