Therapeutic Strategies Targeting the Gut-Bone Axis: The Role of Probiotics and Faecal Microbiota Transplantation

Abstract

The gut microbiota is an important modulator of skeletal homeostasis through immune regulation, microbial metabolite production, intestinal barrier integrity, endocrine signalling and mineral handling. Dysbiosis may contribute to bone loss by increasing intestinal permeability, promoting systemic low-grade inflammation, enhancing osteoclastogenic cytokine activity and reducing bone-protective metabolites, particularly short-chain fatty acids. This narrative review synthesises mechanistic, preclinical and clinical evidence on microbiome-directed strategies targeting the gut-bone axis, with emphasis on probiotics, prebiotics, synbiotics and faecal microbiota transplantation. Experimental studies suggest that selected probiotic strains may influence bone remodelling by increasing short-chain fatty acid production, improving gut barrier function, modulating Treg/Th17 balance and reducing inflammatory bone resorption. Prebiotics and synbiotics may further support skeletal health by enhancing calcium absorption, stimulating beneficial microbial activity and promoting metabolite-mediated regulation of osteoblast and osteoclast function. Human studies provide preliminary evidence for modest improvements in bone mineral content, preservation of bone mineral density and reductions in biochemical markers of bone resorption. However, most trials remain limited by small sample sizes, heterogeneous formulations, short follow-up periods and reliance on surrogate outcomes rather than fracture endpoints. Faecal microbiota transplantation provides useful experimental insight into the causal relevance of microbial communities in host metabolic and skeletal physiology, but its application to osteoporosis remains investigational because donor variability, recipient compatibility, pathogen transmission, long-term ecological stability and regulatory oversight remain unresolved. Overall, targeting the gut-bone axis is biologically plausible and may complement established skeletal care, but current evidence supports further investigation rather than immediate clinical replacement of standard osteoporosis therapies.