Inulin protects against heat stroke-induced intestinal barrier damage through the gut microbiota-butyrate-GPR43 axis, whereby increased butyrate activates GPR43 and upregulates tight junction proteins via PKC-CREB signaling to improve barrier integrity and reduce systemic inflammation.
Four weeks of dietary intervention with 5% inulin decreased core body temperature and mortality in heat-stroke mouse models.
Inulin supplementation reshaped gut microbiota composition and increased Bifidobacterium abundance in heat-stroke mice.
Inulin increased fecal butyrate levels, a short-chain fatty acid that mediates intestinal barrier protection.
Butyrate activated G protein-coupled receptor 43 (GPR43) and upregulated tight junction proteins zonula occludens-1 (ZO-1) and occludin.
The protective mechanism of inulin against heat stroke operates through the gut microbiota-butyrate-GPR43 signaling axis.
This research suggests that inulin, a dietary fiber found in many plants and commonly used as a prebiotic supplement, can protect against heat stroke-related gut damage through a specific biological chain of events. When mice were fed a diet containing 5% inulin for four weeks before being exposed to heat stroke conditions, they had lower body temperatures and better survival rates compared to untreated mice. The researchers traced the protective effect through a series of steps: inulin fed beneficial gut bacteria (particularly Bifidobacterium), which produced more butyrate (a short-chain fatty acid), which then activated a receptor on intestinal cells called GPR43, ultimately strengthening the gut's protective lining. The gut lining normally acts as a barrier that keeps harmful substances from entering the bloodstream. Heat stroke can damage this barrier, allowing bacteria and toxins to leak through and cause widespread inflammation throughout the body. This study found that inulin helps maintain the integrity of this barrier by increasing the production of proteins called ZO-1 and occludin, which act like the 'cement' holding intestinal cells together tightly. These changes were confirmed using multiple scientific techniques including genetic analysis of gut bacteria, chemical analysis of stool samples, protein detection methods, and laboratory cell experiments. This research suggests that consuming inulin as a dietary supplement before periods of heat exposure could potentially help protect the gut and reduce the severity of heat stroke. It provides a detailed biological explanation for how a simple dietary fiber can influence the body's response to extreme heat, pointing toward a possible nutritional strategy to reduce heat stroke risk, particularly relevant for people in hot climates, athletes, or workers exposed to high temperatures.
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Upload Your LabsLuo Z, Wang Z, Tan Y, He G, Li P, Hu X, et al.. (2026). Mechanistic Study of Inulin in Ameliorating Heat Stroke-Induced Intestinal Barrier Damage via Modulation of Gut Microbiota- Butyrate-GPR43 Axis.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.5c13669