Molecular Mechanisms of Short-Chain Fatty Acid-Mediated Gut-Bone Axis in Regulating Fracture Healing and Progress of Integrated Chinese and Western Medicine Interventions

DOI: 10.12201/bmr.202608.00007

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  Abstract: SFracture healing is a complex, multi-stage biological process involving inflammatory response, tissue repair, and bone remodeling, regulated by multiple factors including cellular, molecular, and systemic microenvironmental elements. The gut-bone axis, a key trans-organ regulatory pathway connecting the gut microbiome with bone metabolism, is closely associated with complications such as delayed fracture healing and nonunion when dysfunctional. Short-chain fatty acids (SCFAs), the primary metabolites produced by the anaerobic fermentation of dietary fibers and other substrates by gut microbiota, serve as the core mediators of the gut-bone axis. They can precisely regulate the entire process of fracture healing through direct actions on bone tissue cells or indirect modulation of immune, endocrine, and nutritional metabolic pathways. This article systematically reviews the generation and metabolic characteristics of SCFAs, deeply analyzes the molecular mechanisms by which they mediate the gut-bone axis in regulating fracture healing, and summarizes research progress in both Western medicine–targeted interventions and Traditional Chinese Medicine syndrome differentiation and treatment. It focuses on exploring the synergistic effects and clinical application prospects of integrated Chinese and Western medicine interventions, aiming to provide novel insights and targets for the clinical management of fracture healing, and to offer theoretical support for the integrated prevention and treatment of bone metabolism–related diseases.

  Key words: SShort-chain fatty acids; Gut-bone axis; Fracture healing; Molecular mechanisms; Integrative Chinese and Western medicine interventions

  Submit time: 4 August 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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