Gut dysbiosis and osteoporosis: mechanisms of the gut-bone axis, clinical evidence, and translational strategies
Year: 2026
Type: article
Abstract: Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass, deterioration of bone microarchitecture, and increased susceptibility to fragility fractures. Growing evidence implicates the gut microbiota as an environmental modifier of skeletal homeostasis, giving rise to the concept of the gut-bone axis. Gut dysbiosis may influence bone remodeling through impaired intestinal barrier integrity, microbial-product translocation, immune-inflammatory dysregulation, and altered microbial metabolites, including short-chain fatty acids, bile acids, tryptophan-derived indoles, and trimethylamine N-oxide. These signals may interact with osteoblasts, osteoclasts, immune cells, and endocrine pathways involving estrogen, parathyroid hormone, vitamin D, and calcium handling. Human observational and multi-omics studies support associations between microbial composition or function and bone mineral density, bone turnover, and fracture-related phenotypes, whereas Mendelian randomization can prioritize candidate directional relationships but does not establish clinical causality. Taxonomic findings remain heterogeneous across populations and are influenced by age, menopausal status, diet, geography, medications, comorbidities, and analytical methods. Human probiotic trials show strain- and population-specific skeletal signals together with several null or negative studies; microbiome target engagement is measured infrequently, and mediation of skeletal effects has not been established. Prebiotic, synbiotic, postbiotic, fecal microbiota transplantation, and metabolite- or receptor-directed approaches remain at earlier and heterogeneous stages of translation. Rather than cataloguing individual taxa or pathways, this review organizes the evidence along an evidence-to-translation continuum spanning human observational studies, multi-omics, causal inference, mechanistic experiments, and clinical interventions. It distinguishes human from preclinical evidence and separates skeletal effects from microbiome target engagement and mediation to define the evidence required for reproducible functional biomarkers and mechanism-based adjunctive interventions.
Institution: Cangzhou Central Hospital
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225636090