Combined heat and exercise stress disrupt gut microbiota and promote microbial translocation

The incidence of exertional heat stroke (EHS) has increased markedly in recent decades. Although intestinal barrier dysfunction and gut microbiota alterations are increasingly implicated in EHS pathophysiology, the respective contributions of heat exposure and physical exercise to these processes remain incompletely defined.

Male C57BL/6 mice were assigned to Control (C), Exercise (E), Heat shock (H), or Exercise + Heat shock (HE) groups. Exercise and/or heat exposure were applied to induce exertional heat stress. Intestinal injury and permeability were assessed by histopathology and circulating D-lactate levels. Gut and blood microbial profiles were characterized using 16S rRNA gene sequencing, and associations between microbial signatures and intestinal injury markers were analyzed.

Both heat exposure and exercise induced intestinal injury and increased circulating D-lactate levels, with the most severe effects observed in the combined HE group. Heat exposure was associated with pronounced alterations in gut microbial diversity and community structure, whereas exercise was associated with increased microbial diversity and gut-associated microbial signatures detected in blood samples. Differential abundance analyses revealed distinct taxonomic profiles associated with heat, exercise, and their combination. Correlation analyses demonstrated significant associations between intestinal injury markers and circulating microbial profiles.

These findings indicate that heat exposure and exercise exert distinct yet interacting associations with intestinal barrier integrity and microbial community distribution. Heat stress primarily disrupts gut microbial ecology and barrier function, whereas exercise is more closely associated with increased systemic detection of gut-derived microbial signatures. Together, these results highlight the gut microbiota-barrier axis as a key interface linking environmental and physiological stressors to systemic responses during exertional heat stress.