The Link Between the Gut Microbiome and Bone Metastasis

The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors and extensive blood flow, especially affecting patients with thyroid, prostate, breast, lung, and kidney cancers, where bone metastases severely reduce the quality of life. While the involvement of the gut microbiome in bone metastasis formation is still being explored, proposed mechanisms suggest that intestinal dysbiosis may alter the bone microenvironment via the gut-immune-bone axis, fostering a premetastatic niche and immunosuppressive milieu suitable for cancer cell colonization. Disruption in the delicate balance of bone modeling and remodeling may further create a favorable environment for metastatic growth. This review focuses on the link between beneficial or dysbiotic microbiome composition and bone homeostasis, as well as the role of the microbiome in bone metastasis development. It also provides an overview of clinical trials evaluating the impact of gut microbial community structure on bone parameters across various conditions or health-related issues. Dietary interventions and microbiota modulation via probiotics, prebiotics, and fecal microbiota transplantation help support bone health and might offer promising strategies for addressing bone-related complications in cancer.