Gut Microbiota Dysbiosis in Degenerative Musculoskeletal Diseases: From Pathogenic Mechanisms to Targeted Therapeutic Strategies

Degenerative musculoskeletal diseases, including intervertebral disc degeneration (IDD), osteoporosis, osteoarthritis (OA), and sarcopenia, represent major contributors to pain, disability, and loss of life quality worldwide. Despite substantial advances in biomechanics, genetics, and clinical interventions, the fundamental causes of tissue degeneration and failed repair remain elusive, and disease-modifying therapies are largely unavailable. Recent discoveries have reframed these disorders through the lens of microbial ecology, suggesting that gut microbiota dysbiosis plays a pivotal and previously underestimated role in musculoskeletal homeostasis and degeneration.

The gut–musculoskeletal axis has emerged as an integrative signaling network connecting the intestinal microbiota with distant musculoskeletal tissues. Metabolites such as short-chain fatty acids, secondary bile acids, and urolithins modulate osteoblast and osteoclast differentiation, muscle metabolism, and cartilage anabolism. Conversely, lipopolysaccharide-mediated endotoxemia promotes systemic low-grade inflammation and matrix degradation, while microbiome-derived extracellular vesicles carry microRNAs and proteins that influence nucleus pulposus cell fate and bone remodeling. Gut barrier disruption, often induced by dysbiosis, exacerbates immune activation and propagates a chronic inflammatory loop contributing to muscle atrophy and skeletal deterioration.

Recent studies have revealed profound shifts in gut microbial composition among patients with IDD, OA, and osteoporosis. Microbiome-targeted interventions, ranging from probiotics and prebiotics to fecal microbiota transplantation (FMT) and postbiotic supplementation, have demonstrated promising preventive and therapeutic effects in preclinical models. However, key questions remain unresolved: which microbial taxa and metabolites drive these processes, how microbial signaling integrates with host immunity and metabolism, and to what extent these findings can be translated into clinical therapies. Filling these knowledge gaps requires multidisciplinary efforts integrating microbiology, musculoskeletal biology, immunology, and bioinformatics.

This Research Topic aims to unify mechanistic and translational research on how gut microbiota dysbiosis contributes to the initiation and progression of degenerative musculoskeletal diseases, and how these insights can inform novel microbiome-based therapeutic strategies. By bridging molecular mechanisms with potential clinical applications, this collection seeks to promote a systems-level understanding of gut–musculoskeletal crosstalk and its implications for disease prevention and regeneration.

To gather further insights within this defined landscape, we welcome contributions addressing, but not limited to, the following themes:

o Microbial community profiling in IDD, OA, osteoporosis, and sarcopenia through metagenomics, 16S rRNA sequencing, and multi-omics integration

o The gut–disc axis: dysbiosis-driven nucleus pulposus cell pyroptosis, autophagy, and extracellular matrix (ECM) degradation

o The gut–bone axis: microbiome regulation of osteoblast/osteoclast balance, bone mineral density, and fracture susceptibility

o The gut–joint axis: microbial metabolites and immune circuits in cartilage catabolism and joint inflammation

o The gut–muscle axis: microbial influences on mitochondrial integrity, energy metabolism, and sarcopenic degeneration

o Extracellular vesicles as bidirectional messengers in gut–musculoskeletal communication

o Intestinal barrier dysfunction and endotoxin leakage as triggers of systemic inflammation and tissue damage

o Microbial metabolites (short-chain fatty acids, bile acids, tryptophan derivatives, urolithins) as signaling molecules targeting bone, cartilage, and muscle

o Therapeutic modulation of the microbiome: probiotics, prebiotics, synbiotics, FMT, diet, or postbiotics for restoring musculoskeletal homeostasis

o Microbiota-derived biomarkers for early diagnosis, prognosis, and personalized therapy in musculoskeletal diseases

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: gut microbiota, dysbiosis, osteoarthritis, intervertebral disc degeneration, osteoporosis

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.