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Objectives To systematically review and quantitatively synthesize observational evidence on gut microbiota alterations in adults with osteoporosis, osteopenia or low bone mineral density, with particular emphasis on α-diversity, β-diversity and taxonomic composition. Methods A systematic search of PubMed, Embase, Web of Science, the Cochrane Library and EBSCO were conducted for studies published between 1 June 2012 and 31 December 2025. Observational studies comparing adults with osteoporosis, osteopenia or low bone mineral density against controls and using fecal microbiome sequencing were eligible. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled for extractable α-diversity outcomes. β-diversity findings and taxonomic differences were synthesized descriptively. Methodological quality was assessed using a modified Newcastle–Ottawa Scale. Results Eighteen studies were included in the systematic review and 15 contributed to the quantitative synthesis, representing 2,851 participants (1,094 cases/abnormal bone mass and 1,757 controls). Meta-analysis showed no significant overall differences in the Shannon index (SMD = 0.27, 95% CI: −0.03 to 0.57; I 2 = 81.8%) or the Chao1 index (SMD = −0.13, 95% CI: −0.82 to 0.55; I 2 = 85.4%). Descriptive synthesis of β-diversity more often suggested structural differences in gut microbial communities between case groups and controls. At the taxonomic level, Bacteroides was more frequently enriched in case groups, whereas evidence for several other genera, including Blautia , was less consistent. Direction-of-effect synthesis further indicated recurrent enrichment of Bacteroides and Lactobacillus in case groups and more frequent enrichment of Roseburia in controls. Overall study quality was moderate to high. Conclusions This review reveals that osteoporosis and abnormal bone mass present no significant differences in gut microbial alpha-diversity, but exhibit distinct β-diversity and consistent taxonomic alterations. Gut dysbiosis is potentially associated with compromised bone health; nevertheless, marked heterogeneity persists, necessitating further standardized studies to validate clinically valuable microbial signatures. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261382643 , identifier CRD420261382643.
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Cao et al. (2026) studied this question.
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