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

Area of Science:

• Pediatric Endocrinology
• Molecular Biology
• Exosome Biology

Background:

• Idiopathic short stature (ISS) presents a significant pediatric challenge with unknown etiology and variable growth hormone (GH) treatment response.
• Plasma exosomes in children with ISS show increased levels of human sequence A-microRNA-17-3p (hsa-miR-17-3p).
• This microRNA disrupts crucial growth signaling pathways and impairs cartilage cell proliferation.

Purpose of the Study:

• To investigate the role of exosomal hsa-miR-17-3p in ISS pathogenesis.
• To explore potential environmental triggers, such as dietary factors, contributing to ISS.
• To develop and test novel therapeutic strategies for ISS.

Main Methods:

• Analysis of plasma exosome content (hsa-miR-17-3p) in children with ISS.
• Development of a capsaicin-rich diet rat model mimicking ISS.
• Assessment of gut inflammation and exosome miRNA profiles in rats and ISS children.
• In vivo testing of engineered exosomes to silence hsa-miR-17-3p combined with GH therapy.

Main Results:

• Elevated hsa-miR-17-3p in plasma exosomes of ISS children suppresses ZNF148/SOS1 signaling.
• Capsaicin-rich diet in rats induced ISS-like phenotype with increased plasma hsa-miR-17-3p and gut inflammation.
• ISS children's fecal samples showed elevated hsa-miR-17-3p and inflammatory markers, suggesting a link to spicy diets.
• Combined therapy with engineered exosomes and GH restored growth plate function.

Conclusions:

• A diet-driven exosome axis involving hsa-miR-17-3p contributes to ISS.
• Dietary factors, particularly capsaicin, may trigger gut inflammation and subsequent exosome alterations leading to ISS.
• Targeted exosome-based therapies offer a promising new strategy for managing ISS, especially in regions with high capsaicin consumption.