Glucagon-like peptide-1: a critical link between gut microbiota dysbiosis and degenerative musculoskeletal diseases

Degenerative musculoskeletal diseases are characterized by the progressive loss of structural integrity and functional capacity in muscles, bones, joints, and other related tissues. These conditions primarily include osteoarthritis, osteoporosis, sarcopenia, and intervertebral disc degeneration. These diseases progress gradually, leading to chronic pain, impaired mobility, and a significantly elevated risk of disability. Given their high prevalence and substantial health burden, degenerative musculoskeletal diseases pose a major challenge in the context of population aging. Although various types of degenerative musculoskeletal diseases affect different primary tissues, they share common pathological features including chronic inflammation, oxidative stress, and dysregulated cell death. These shared mechanisms imply the existence of a common molecular regulatory network. Glucagon-like peptide-1 (GLP-1), a peptide secreted under the regulation of the gut microbiota (GM), has garnered increasing attention for its protective roles in bone, cartilage, muscle, and intervertebral disc tissues. GLP-1 reduces inflammation, mitigates oxidative stress, inhibits apoptosis, and supports microbial homeostasis. This review outlines the mechanisms through which the GM regulates GLP-1 secretion. It further summarizes the core functions and disease-specific pathways by which GLP-1 confers protection against degenerative musculoskeletal diseases. Finally, it explores potential therapeutic strategies targeting the "GM-GLP-1" axis, highlighting microbiota modulation and GLP-1 pathway enhancement as promising treatment approaches for degenerative musculoskeletal diseases.