The gastrointestinal model of heat stroke, states that during prolonged exercise in the heat, blood is diverted from the hepato-splanchnic tissue in the intestine towards the skeletal muscle and skin causing gut ischaemia. Ischaemia of the gut caused by the sudden reduction in blood flow leads to the breakdown of the gastrointestinal barrier. The physical structure is formed by the gut epithelium, which lines the luminal layer of the gut with a series of para-cellular tight junctions. The compromised gastrointestinal barrier increases permeability of the epithelial tight junctions which allow gram negative bacteria to translocate across the gut barrier into the portal circulation where it is transported to the liver. Lipopolysaccharide is located in the walls of the gram negative bacteria; these bacteria are usually contained within the intestinal lumen by the gastrointestinal barrier however, in conditions of augmented permeability the entry of these bacteria into the systemic circulation has been shown to induce an inflammatory response i.e., endotoxemia. Within research intestinal permeability is typically assessed using the urinary ratio of orally administered non digestible, non-metabolised probes, typically lactulose (paracellularly) and L-rhamnose (transcellularly). Research indicates that intestinal permeability can be influenced by endogenous oestrogen – a key ovarian hormone that fluctuates throughout the menstrual cycle. It is thought that oestrogen acts through oestrogen receptors found in the nucleus of the cell which potentiates the tight junction protein occludin which increases the adhesion of the tight junctions. Therefore, theory would suggest that intestinal permeability will fluctuate across the menstrual cycle with changes in oestrogen concentration. Oral contraceptives downregulate endogenous oestrogen production and instead provide an exogenous version (ethinyl-estradiol) which mimics the effects of oestrogen in the body. These reductions in endogenous oestrogen may increase intestinal permeability.

To conclude, this talk will summarise research examining the influence of sex differences including ovarian hormone fluctuations across the menstrual cycle and hormonal contraceptives have on intestinal permeability and implications for women in heat stress.