Leach, Shoji, Allsop, Ellie, Martin, Isobel, Francis, Thomas, Harridge, Stephen, Flood, Tess, McKenna, Zachary, Halket, John, Caldwell, Anna, Sheikh, Nabeel, Rodriguez-Mateos, Ana and Foster, Josh (2026) Sex differences in gastrointestinal permeability during acute uncompensable heat stress: role of menstrual phase hormones. Experimental Physiology. ISSN 0958-0670 (In Press)

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Abstract

Hyperthermia can increase gastrointestinal permeability, allowing microbes to leak from the intestinal lumen to the hepatic portal and systemic circulation. However, the extent to which sex and menstrual cycle hormones impact the risk of increased gastrointestinal permeability during heat stress is unclear. 24 healthy young adults (12-male, 24±3 years; 12-female [5 oral contraceptive users], 23±2 years) participated in the study. Participants first completed a control trial (no heat or exercise) to determine baseline gastrointestinal permeability. Then, participants took part in a hyperthermia trial, where deep body temperature increased by +1.5 °C from baseline via a water perfused suit combined with semi-recumbent cycling at 40 W. Oestradiol was measured at baseline during the hyperthermia trial. In both trials, permeability was assessed by measuring the urinary excretion of orally ingested sucrose (10g) and lactulose/rhamnose ratio (L/R, 1g each) to assess gastroduodenal and small intestine permeability, respectively. Data are presented as the change in excretion from control to hyperthermia. Pooled analysis of all participants identified that hyperthermia increased small intestinal permeability (ΔL/R = 0.012 ± 0.029 [95%CI 0.000 to 0.025], p = 0.050, d_z = 0.43). While there were no sex differences at the group level, we identified a strong positive correlation between ΔL/R and baseline oestradiol concentration within females (r = 0.709, p = 0.040). Gastroduodenal permeability did not increase with hyperthermia (p = 0.136), nor were there any differences between the sexes (p = 0.411). Future studies should confirm whether oestradiol plays an independent role in modulating heat-induced gastrointestinal permeability in humans.

Item Type:	Article
Subjects:	Medicine and health > Clinical medicine Medicine and health
Date Deposited:	12 Nov 2026
Dates:	Date Publication status 27 October 2026 Accepted
School, department or research centre:	School of Human and Social Sciences
URI:	https://repository.uwl.ac.uk/id/eprint/15788
Sustainable Development Goals:	Goal 10: Reduced Inequalities	Sustainable Development Goals:	Goal 13: Climate Action

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