Gut Microbial Metabolites as a Bridge in Osteoporotic Rehabilitation for the Elderly: From Aging-Related Dysbiosis to Precision Non-Pharmacological Strategies.

Background and Objective: Osteoporosis in the elderly represents a major public health challenge in aging societies. Although non-pharmacological rehabilitation has become a core intervention strategy, standard protocols yield highly variable responses across individuals. This review aims to systematically examine the bridging role of gut microbial metabolites in the pathogenesis and rehabilitation of osteoporosis in the elderly, explore the hypothesis that baseline microbial status influences the heterogeneity of rehabilitation outcomes, and propose a microbiota-targeted precision rehabilitation framework for older populations. Methods: This narrative review systematically searched PubMed, Web of Science, Embase, Cochrane Library, Scopus, and CINAHL databases (January 2016 to May 2026). Original studies and reviews on naturally aged animal models and populations aged ≥60 years were included, with 56 articles retained for narrative synthesis. Key Findings: Aging drives gut dysbiosis characterized by depletion of short-chain fatty acid (SCFA)-producing bacteria, accumulation of lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), and disrupted bile acid metabolism. These alterations compromise intestinal barrier integrity and induce chronic low-grade inflammation, ultimately shifting the osteoblast-osteoclast balance toward bone resorption. Exercise training and dietary fiber supplementation can partially reverse these changes by elevating SCFA levels, suppressing NF-κB-mediated inflammatory pathways, and restoring intestinal barrier function. However, the translational gap between animal models and elderly populations, confounding effects of polypharmacy, poor long-term adherence, and inter-individual baseline differences constitute major barriers to translating mechanistic evidence into clinical rehabilitation. Clinical Implications: Baseline gut microbial status may be a core predictor of rehabilitation response, though this hypothesis requires prospective cohort validation. A stratified rehabilitation strategy based on microbial typing-"sensitive" individuals receiving standard protocols and "resistant" individuals receiving combined microbiome-targeted adjunctive therapy (including specific probiotic strains or synbiotics)-offers an actionable research direction for precision rehabilitation. Candidate stratification biomarkers such as the fecal SCFA-to-calprotectin ratio require prospective validation, and the development of home-detectable biomarkers remains a critical translational priority. The clinical translation of this framework depends on the accumulation of long-term follow-up data and the resolution of implementation barriers in real-world primary care settings. Notably, the mechanistic evidence underpinning this framework derives predominantly from animal and in vitro studies (high mechanistic certainty, low translational certainty), whereas clinical trial evidence remains limited to small, short-term, predominantly exploratory trials (low to moderate certainty for efficacy, very low for precision targeting); prospective clinical validation is therefore essential before routine implementation.