Frontiers in Microbiology · Nov 2, 2026
Gut Microbiome in Postmenopausal Osteoporosis: A Case-Control Study
By Linfeng Gao, Shujun Ren
Objective: This frequency-matched case-control study aimed to investigate the association between gut microbiota composition and bone mineral density (BMD) in postmenopausal women, to identify microbial features associated with postmenopausal osteoporosis (PMOP) for hypothesis generation. Methods: A total of 206 postmenopausal women were consecutively enrolled and categorized into an osteoporosis group (n=103) and a normal bone mass control group (n=103) based on dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine and hip. Controls were frequency-matched to cases by age (±1 year), BMI (±1 kg/m²),and years since menopause (±1 year) at the group level through consecutive selection windows; no individual case – control pairing was retained. Fecal samples were collected for 16S rRNA gene sequencing to assess alpha and beta diversity and to compare differential microbial abundances. Serum levels of bone metabolic markers were also measured. Statistical analyses included correlation assessments and multivariate logistic regression to evaluate the gut microbiota-BMD relationship. Results: Significant reductions in the Shannon and Simpson indices were observed in the osteoporosis group compared to the control group (all P<0.05). Furthermore, beta diversity analysis indicated a distinct separation in microbial community structure between the two groups (P=0.002). At the phylum level, the osteoporosis group demonstrated a significantly lower relative abundance of Firmicutes, a higher relative abundance of Bacteroidetes, and a consequently reduced Firmicutes/Bacteroidetes (F/B) ratio (all P<0.05). At the genus level, the relative abundances of Bifidobacterium and Lactobacillus were significantly decreased, whereas Bacteroides and Clostridium were significantly enriched in the osteoporosis group (all P<0.05). Correlation analyses showed positive associations between the abundances of Bifidobacterium and Lactobacillus with lumbar spine and hip BMD (r=0.382-0.456, all P<0.05). In contrast, the abundances of Bacteroides and Clostridium were negatively correlated with BMD (r=-0.315 to -0.397, all P<0.05). Multivariate logistic regression identified a low F/B ratio (OR=3.180,95%CI:1.845–5.482) and reduced Bifidobacterium abundance (OR=2.850,95%CI:1.628 – 4.989) as independent associated factors for PMOP (all P<0.05). Conclusion: Significant gut microbiota dysbiosis is present in postmenopausal women with osteoporosis, characterized by diminished microbial diversity, reduced beneficial bacterial taxa, and enrichment of potentially detrimental genera.