Biological Sex Differences in Heat Acclimation and Gut Microbiome Responses
Authors: Szymanski Michael , Struder Jeb , Thornton Staci , Sekiguchi Yasuki , Stearns Rebecca , Huggins Robert , Casa Douglas 
Published: May 2024

Purpose: Our broad aim was to elucidate the relationship between gut microbiome (gMB) and heat tolerance/acclimation. In this study, we hypothesized that the gMB is affected by acute exercise-heat stress/acclimation and is biologically sex-specific. Methods: Physically active men (M: n=10, 21±2yo, VO2max 51.8±6.6mL−1·kg−1·min−1) and women (W: n=6, 26±5yo, VO2max 45.5±8.0mL−1·kg−1·min−1) completed a modified heat tolerance test (HTT; 65% vVO2max, 2% grade treadmill run, 40°C, 40% relative humidity) until rectal temperature reached 39.5°C (TT39.5) or failure before (preHA) and after (postHA) a 5-day heat acclimation (HA). DNA from stool samples was sequenced via 16S rRNA (V4). a-diversity (Shannon Index) and rarified abundances of phyla, family, and genus were calculated by subsampling to 10,000 reads per sample. Blood inflammation markers were measured with commercially available kits. Significant differences (p≤0.05) were determined by nonparametric analyses for gMB indices and parametric analyses for all other variables were reported as mean ± standard deviation and Z scores for compared groups. Results: All subjects acclimated, but W were more resilient to HTT pre and postHA (preHA TT39.5: 29.14±7.14min (M), 35.02±3.67min (W), p=0.042; postHA TT39.5: 31.11±5.61min (M), 38.13±3.14min (W), p<0.01). gMB changes were observed among all subjects with reductions in Peptostreptococcaceae and Proteobacteria at postHA (vs. preHA, p<0.05). Comparison of W and M revealed marked differences. M had lower (vs. W) Christensenella (Z=-2.119, p=0.034), Erysipelotrichaceae (Z=-2.495, p=0.013) and higher Lactococcus (Z=-2.254, p=0.024), Peptostreptococcaceae (Z=-2.386, p=0.017), Pasteurellaceae(Z=-2.210, p=0.027), and Haemophilus (Z=-2.210, p=0.027) preHA. PostHA, M had lower (v. W) Eggerthella (Z=-2.022, p=0.043), Family XIII (Z=-2.025, p=0.043), Erysipelotrichaceae (Z=-2.061, p=0.039), Oxalobacteraceae (Z=-2.445, p=0.014), and higher Peptostreptococcaceae (Z=-2.173, p=0.030) with no differences in Shannon Index. Biomarkers IL-1β and IFN-γ were increased postHA (v. preHA, p<0.05), but W had distinct I-FABP (decreased v. M, p<0.05) and IFN-γ (increased v. M, p<0.05) responses. Conclusion: gMB changes during heat acclimation include bacteria associated with heat stress responses in previous literature. W and M differ in gMB, acute heat tolerance, and acclimation responses with concomitant sex differences in inflammatory and metabolite markers potentially related to gMB. Ongoing research investigates associations of targets such as Proteobacteria with previous findings related to heat tolerance and acclimation and metabolite patterns in systemic circulation associated with bacterial species significantly affected by HA. DoD BA200299. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.