Gut microbiota modulation in the prevention and treatment of heat stroke

In recent years, heat stroke (HS) have been reported with increasing frequency, and this trend is hard to separate from broader environmental changes, including climate change, recurrent extreme heat events, and air pollution. When people are exposed to high-temperature environments for a prolonged period, especially during intense physical activity, the condition may progress to HS. HS is an acute and potentially fatal disorder that can deteriorate rapidly if not treated in time. The intestine appears to be particularly vulnerable during HS. HS can disrupt intestinal tight junctions and weaken the barrier function of the gut, leading to what is commonly described as a "leaky gut." Once this barrier is compromised, microbial products such as lipopolysaccharides can enter the bloodstream. These molecules may then activate immune cells, promote excessive cytokine release, and eventually drive a systemic inflammatory response. In severe cases, this inflammatory process can develop into systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Current evidence increasingly suggests that intestinal injury is not simply a secondary result of HS. Rather, it may serve as an important early event in the development and progression of the disease. Still, it should be noted that much of the available evidence comes from preclinical studies, and strong clinical confirmation is still limited. Probiotics have attracted attention because they may help reduce the occurrence and severity of HS by maintaining gut microbiota balance and regulating intestinal immune responses. However, since most supporting data are still derived from animal experiments, their protective effects in humans need to be interpreted carefully. Another point worth emphasizing is that the gut is not working alone. Through gut-organ communication networks, the intestinal microbiota can interact with distant organs, including the liver, lungs, and brain. These gut-liver, gut-lung, and gut-brain axes may help explain how HS leads to injury beyond the intestine itself. In this review, we summarize current findings on how modulation of the gut microbiota may improve intestinal thermotolerance and strengthen barrier function, with the aim of providing useful insights for the prevention and treatment of HS in clinical practice.