The gut microbiota has emerged as a key regulator of endocrine, metabolic, and immune homeostasis, influencing numerous physiological processes beyond the gastrointestinal tract. Growing evidence supports the existence of a dynamic gut–bone axis, through which microbial communities and their metabolites regulate bone remodeling, mineral metabolism, and skeletal integrity. These interactions are mediated by endocrine pathways involving vitamin D, parathyroid hormone, sex steroids, insulin-like growth factor-1, and other systemic regulators that coordinate osteoblast and osteoclast activity. Disruption of the gut microbiome has been linked to osteoporosis, inflammatory bone loss, impaired fracture healing, and other metabolic bone disorders. More recently, the gut microbiota has also been implicated in the development of bone metastases, where microbial dysbiosis may influence systemic metabolism, endocrine signaling, tumor progression, and the establishment of the bone metastatic niche. Advances in microbiome profiling, metabolomics, multi-omics technologies, and experimental models are providing new insights into the complex interactions between the gut microbiome, endocrine regulation, skeletal biology, and cancer.

Despite rapid progress in this field, many of the mechanisms underlying gut microbiota–bone interactions remain incompletely understood, particularly in the context of endocrine regulation and bone metastasis. Improved understanding of these pathways may reveal novel biomarkers and microbiome-targeted therapeutic strategies for preventing skeletal disease, preserving bone health, and limiting metastatic progression within bone. This Research Topic aims to bring together basic, translational, and clinical studies that advance our understanding of the gut–bone axis across metabolic bone disease and bone metastasis. By integrating expertise from endocrinology, bone biology, microbiology, and oncology, this collection seeks to highlight emerging mechanisms and therapeutic opportunities that improve skeletal health and patient outcomes.

We welcome contributions addressing, but not limited to, the following themes:

• Endocrine regulation of the gut–bone axis
• Gut microbiota and bone remodeling in health and disease
• Microbial regulation of calcium, phosphate, and vitamin D metabolism
• Microbial metabolites regulating osteoblast and osteoclast function
• Gut microbiota in osteoporosis and other metabolic bone disorders
• Gut microbiota and fracture healing
• Gut microbiota and the development of bone metastases
• Microbiome-driven regulation of the bone metastatic niche
• Multi-omics approaches, microbiome profiling, and biomarkers of the gut–bone axis
• Probiotics, prebiotics, dietary interventions, and microbiome-targeted therapies for skeletal diseases and bone metastases

Are you interested in contributing a manuscript to this Research Topic?

Gut Microbiota in Bone Metabolism, Disease, and Bone Metastasis