Gastrointestinal microbiota and barrier integrity in individuals who develop exertional heat illness and pair-matched controls: A prospective observational cohort study.

It has been hypothesised that the composition of the gastrointestinal (GI) microbiota contributes to exertional heat illness (EHI) aetiology, but relevant empirical data in humans are lacking. Utilising a unique prospective study design, stool samples and resting blood samples were obtained from 550 individuals prior to (within 3 days) undertaking a 6.4-mile/10.3 km loaded march (median (IQR) duration = 66 (1) min), during which 79 individuals developed an EHI (mild, n = 55; severe, n = 24). These individuals were pair-matched for body mass index and cardiorespiratory fitness to individuals who did not develop an EHI during the same exercise (non-EHI). Our primary outcome measure was the composition of the gut microbiota, determined using 16S ribosomal RNA (rRNA) amplicon sequencing of stool samples. Secondary outcomes included the concentration of baseline blood biomarkers of GI barrier integrity (intestinal fatty acid binding protein, claudin 3, zonulin, lipopolysaccharide binding protein, and soluble cluster of differentiation 14). No significant differences in the composition of the GI microbiota (α-diversity, β-diversity, relative abundance, differential abundance) were observed between EHI cases and matched non-EHI controls (P > 0.05). Similarly, no significant between-group differences in biomarkers of GI barrier integrity were observed. These findings persisted when conducting additional sub-group analysis of severe EHI cases only, and additional sensitivity analysis excluding individuals who reported non-steroidal anti-inflammatory drug use and/or GI disorders. In conclusion, when potential confounding factors are controlled for, the composition of the GI microbiota and baseline GI barrier integrity do not appear to predispose to increased EHI risk during strenuous exercise.