Stress and the gut-brain axis: Cognitive performance, mood state, and biomarkers of blood-brain barrier and intestinal permeability following severe physical and psychological stress.

BACKGROUND: Physical and psychological stress alter gut-brain axis activity, potentially causing intestinal barrier dysfunction that may, in turn, induce cognitive and mood impairments through exacerbated inflammation and blood brain barrier (BBB) permeability. These interactions are commonly studied in animals or artificial laboratory environments. However, military survival training provides an alternative and unique human model for studying the impacts of severe physical and psychological stress on the gut-brain axis in a realistic environment. PURPOSE: To determine changes in intestinal barrier and BBB permeability during stressful military survival training and identify relationships between those changes and markers of stress, inflammation, cognitive performance, and mood state. MATERIALS AND METHODS: Seventy-one male U.S. Marines (25.2 ± 2.6 years) were studied during Survival, Evasion, Resistance, and Escape (SERE) training. Measurements were conducted on day 2 of the 10-day classroom phase of training (PRE), following completion of the 7.5-day field-based simulation phase of the training (POST), and following a 27-day recovery period (REC). Fat-free mass (FFM) was measured to assess the overall physiologic impact of the training. Biomarkers of intestinal permeability (liposaccharide-binding protein [LBP]) and BBB permeability (S100 calcium-binding protein B [S100B]), stress (cortisol, dehydroepiandrosterone sulfate [DHEA-S] epinephrine, norepinephrine) and inflammation (interleukin-6 [IL-6], high-sensitivity C-reactive protein [hsCRP]) were measured in blood. Cognitive performance was assessed by psychomotor vigilance (PVT) and grammatical reasoning (GR) tests, and mood state by the Profile of Mood States (total mood disturbance; TMD), General Anxiety Disorder-7 (GAD-7), and Patient Health (PHQ-9) questionnaires. RESULTS: FFM, psychomotor vigilance, and LBP decreased from PRE to POST, while TMD, anxiety, and depression scores, and S100B, DHEA-S, IL-6, norepinephrine, and epinephrine concentrations all increased (all p ≤ 0.01). Increases in DHEA-S were associated with decreases in body mass (p = 0.015). Decreases in FFM were associated with decreases in LBP concentrations (p = 0.015), and both decreases in FFM and LBP were associated with increases in TMD and depression scores (all p < 0.05) but not with changes in cognitive performance. Conversely, increases in S100B concentrations were associated with decreases in psychomotor vigilance (p < 0.05) but not with changes in mood state or LBP concentrations. CONCLUSIONS: Evidence of increased intestinal permeability was not observed in this military survival training-based model of severe physical and psychological stress. However, increased BBB permeability was associated with stress and cognitive decline, while FFM loss was associated with mood disturbance, suggesting that distinct mechanisms may contribute to decrements in cognitive performance and mood state during the severe physical and psychological stress experienced during military survival training.

Threshold of Energy Deficit and Lower-Body Performance Declines in Military Personnel: A Meta-Regression.

BACKGROUND: Negative energy balance (EB) is common during military operations, diminishing body mass and physical performance. However, the magnitude of negative EB where performance would still be maintained is not well defined. OBJECTIVE: Our objective was to explore relationships between EB and physical performance during military operations and define an acceptable negative EB threshold where performance may be maintained. METHODS: A systematic search was performed for studies that measured EB and physical performance during military training. A total of 632 articles and technical reports were screened. Lower-body power and strength were the most common performance tests across investigations and were used as physical performance outcomes. Data were extracted from nine eligible studies containing 15 independent subgroups. Meta-regression assessed changes in performance in relation to study duration (days), average daily EB, and total EB (daily EB × duration). RESULTS: Changes in physical performance were not associated with average daily EB or training duration. Total EB was associated with changes in lower-body power (r2 = 0.764, P < 0.001) and strength (r2 = 0.836, P < 0.001) independently and combined (r2 = 0.454, P = 0.002). Predictive equations generated from the meta-regression indicated that, for a zero to small (2%) decline in performance, total EB should be limited to - 5686 to - 19,109 kcal, for an entire operation, whereas total EB of - 39,243 to - 59,377 kcal will result in moderate (7%) to large (10%) declines in performance. CONCLUSION: These data demonstrated that greater total negative EB is associated with declines in lower-body performance during military operations.