Comprehensive profiling of gut microbiota in postmenopausal osteoporosis

<h4>Background/aim</h4>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.<h4>Materials and methods</h4>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.<h4>Results</h4>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 <i>Faecalibacterium prausnitzii</i>, <i>Anaerostipes faecalis</i>, and <i>Lactonifactor longoviformis</i>, were significantly reduced in the osteoporosis group. <i>F. prausnitzii</i> abundance was positively correlated with the femoral neck T-score (r = 0.41, p = 0.018), whereas <i>Oxobacter pfennigii</i> showed a negative correlation with lumbar spine BMD (r = -0.43, p = 0.015).<h4>Conclusion</h4>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.