The interface of a leaky gut with neuromuscular junction degradation; implications for severe sarcopenia

Introduction: A pathological increase in intestinal permeability or leaky gut is recently implicated in the pathogenesis of age-associated muscle loss, termed sarcopenia. However, the associated myotoxic effects are poorly known. We investigated the associations of a leaky gut with neuromuscular junction (NMJ) degradation in the context of severe sarcopenia and functional compromise in older adults.

Methodology: This study includes controls (n=161, age=73.4±8.5 years) and severe sarcopenic men (n=148, age=72.4±7.2 years) for measurements of plasma markers of a leaky gut (zonulin), NMJ degradation (CAF22), and bacterial load (lipopolysaccharides-binding protein; LBP). We also measured handgrip strength (HGS), gait speed, and short physical performance battery (SPPB) as sarcopenic and functional compromise markers, respectively.

Results: Severe sarcopenic patients had higher plasma zonulin, CAF22, and LBP levels and lower HGS, gait speed, and SPPB scores than controls (all p<0.05). We found significant correlations between plasma zonulin and CAF22 in controls and severe sarcopenic men (both p<0.05). The presence of severe sarcopenia and SPPB scores < 9 were associated with strengthening the correlation between zonulin and CAF22 (p<0.05). Higher plasma zonulin and CAF22 were associated with higher plasma LBP, lower HGS and gait speed, and lower SPPB scores (all p<0.05).

Conclusion: Collectively, severe sarcopenia and functional compromise due to intestinal leak may involve NMJ degradation and higher plasma bacterial load. Future studies should establish the causal and mechanistic associations between intestinal leak and sarcopenia in old age.