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

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.