Hyperthermia-induced endotoxemia resulting from elevated gut permeability is amongst the main factors linked to the development of exertional heat stroke. Gastrointestinal ischaemia resulting from elevated heat stress could disrupt the integrity of endothelial tight junctions. The integrity of endothelial tight junctions is heavily influenced by the composition of the intestinal microbiota. Alterations in gut microbiota composition may affect gut permeability and the translocation of substances across the gastrointestinal barrier. While thermal stress is known to disturb gut microbiota function, it remains uncertain if endotoxemia triggered by an acute bout of exertional heat stress can be contributed by perturbations in gut microbiota composition. As such, the impact of gut microbiota modulation on hyperthermia-induced endotoxemia and its associated CNS symptoms is an idea worthy of future investigations.