Sex Differences in Immune and Gut Microbiota Responses to Military Training

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PURPOSE: Military training includes multiple stressors that together may increase risk for illness by degrading immune function and altering gut microbiota. However, whether sex differences exist in those responses is undetermined. This study aimed to determine immune and gut microbiota responses during military training and identify sex differences in those responses. METHODS: Seventy-two military cadets (33% female) participated in an arduous 17-d training event. Blood, saliva, and stool were collected upon beginning (PRE) and completing (POST) training. Immune function was assessed by salivary secretory IgA (SIgA), latent virus reactivation, peripheral leukocyte distribution, circulating cytokines, and mitogen-stimulated cytokine profiles. Gut microbiota composition was assessed by 16S rRNA amplicon sequencing. RESULTS: Participants experienced a ~4% body weight loss and sex-independent increases in concentrations of cortisol, myoglobin, catecholamines, and multiple cytokines. The granulocyte-to-lymphocyte ratio increased and SIgA decreased PRE to POST in males but not females ( Pinteraction ≤ 0.02). Mitogen-stimulated cytokine profiles were generally reduced at POST versus PRE independent of sex. No differences in virus reactivation were observed. Sex differences in gut microbiota responses were limited to Bifidobacterium and Ruminococcus , which increased in males relative to females (log 2 fold change (FC) = 2.0-2.4; qinteraction = 0.19). Independent of sex, 24 genera differed at POST versus PRE with Lactobacillus demonstrating the largest decrease (log 2 FC = -0.90; qtime = 0.02) and Veillonella the largest increase (log 2 FC = 1.09; qtime = 0.03). Multiple correlations between markers of stress, immune function, and gut microbiota composition were observed ( q ≤ 0.15). CONCLUSIONS: Immune redistribution, leukocyte compromise, and interrelated changes in gut microbiota composition were evident within this training environment. Those responses demonstrated associations with markers of stress severity but also sex differences, suggesting a more pronounced depression of immune function in males.

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