Capsaicin diet drives gut inflammation and exosomal miR-17-3p elevation in idiopathic short stature.

Summary

This translational study links a capsaicin-rich diet to idiopathic short stature via exosomal miR-17-3p that suppresses ZNF148/SOS1 signaling and impairs chondrocyte proliferation. A rat model recapitulated the phenotype with normal GH/IGF-1 but elevated exosomal miR-17-3p and gut inflammation, and engineered anti–miR-17-3p exosomes plus local GH restored growth plate function.

Key Findings

• Exosomal hsa-miR-17-3p is elevated in children with idiopathic short stature and suppresses ZNF148/SOS1 signaling, impairing growth signaling and chondrocyte proliferation.
• A capsaicin-rich diet in rats induces mild gut inflammation and increases miR-17-3p in intestinal and plasma exosomes with normal GH/IGF-1 levels, recapitulating ISS-like features.
• Engineered anti–miR-17-3p exosomes combined with local growth hormone restored growth plate function in preclinical models.
• Fecal samples from ISS children showed elevated miR-17-3p and inflammatory markers, linking spicy diets to ISS pathogenesis.

Clinical Implications

While not practice-changing yet, the study suggests assessing dietary capsaicin exposure and considering exosomal miR-17-3p as a biomarker for ISS risk stratification. It also motivates clinical trials testing dietary modification and miR-17-3p–targeted strategies alongside GH therapy.

Limitations

• Human component lacks detailed sample size and is observational, limiting causal inference.
• Generalizability across diverse diets and populations is uncertain; preclinical therapeutic data require clinical translation.

Future Directions

Prospective dietary-intervention trials in ISS-prone regions; validation of exosomal miR-17-3p as a biomarker; early-phase trials of miR-17-3p–targeting strategies in combination with GH.