The molecular basis of sarcopenia in inflammatory bowel disease: from gut-muscle axis to therapeutic opportunities

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, represents a significant yet underrecognized extraintestinal manifestation of inflammatory bowel disease (IBD). Imaging techniques such as dual-energy X-ray absorptiometry (DXA), computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound, combined with functional performance tests, offer promising strategies for early diagnosis. However, elucidating the molecular drivers of muscle wasting remains crucial. In IBD, chronic systemic inflammation, gut microbiota dysbiosis, and malnutrition synergistically disrupt muscle homeostasis by activating catabolic pathways and suppressing anabolic signals. Key molecular mechanisms involve NF-κB and JAK/STAT3 activation, inhibition of the IGF-1/mTOR axis, and alterations in microbiota-derived metabolites. Emerging evidence supports the existence of a gut-muscle axis, mediating the systemic effects of intestinal dysbiosis on skeletal muscle integrity. This review provides a comprehensive analysis of the molecular drivers of IBD-associated sarcopenia and explores potential therapeutic interventions targeting the gut-muscle interplay to improve clinical outcomes.