Mechanistic Study of Inulin in Ameliorating Heat Stroke-Induced Intestinal Barrier Damage via Modulation of Gut Microbiota- Butyrate–GPR43 Axis

Abstract

This study investigated how the prebiotic inulin protects against heat-stroke-induced intestinal barrier damage. A classic/passive heat-stroke model was established in C57BL/6J mice. After 4 weeks of dietary intervention with 5% inulin, gut microbiota, fecal short-chain fatty acids, intestinal barrier function, and signaling pathways were examined using 16S rRNA sequencing, gas chromatography–mass spectrometry, Western blotting, and cell models. Inulin decreased the core body temperature and mortality, reshaped the gut microbiota, and increased Bifidobacterium abundance and fecal butyrate. Butyrate activated G protein-coupled receptor 43 (GPR43) and upregulated the tight junction proteins zonula occludens-1 and occludin through protein kinase C-cAMP response element-binding protein signaling, thereby improving barrier integrity and reducing systemic inflammation. These findings indicate that inulin protects against heat stroke through the gut microbiota-butyrate-GPR43 axis and may offer a nutritional intervention strategy.