The magnitude, temporal dynamics, and physiological effects of intestinal microbiome responses to physiological stress are poorly characterized. This study used a systems biology approach and a multiple-stressor military training environment to determine the effects of physiological stress on intestinal microbiota composition and metabolic activity, as well as intestinal permeability (IP). Soldiers ( = 73) were provided three rations per day with or without protein- or carbohydrate-based supplements during a 4-day cross-country ski-march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62 ± 57% (mean ± SD, < 0.001) during STRESS independent of diet group and was associated with increased inflammation. Intestinal microbiota responses were characterized by increased α-diversity and changes in the relative abundance of >50% of identified genera, including increased abundance of less dominant taxa at the expense of more dominant taxa such as Changes in intestinal microbiota composition were linked to 23% of metabolites that were significantly altered in stool after STRESS. Together, pre-STRESS Actinobacteria relative abundance and changes in serum IL-6 and stool cysteine concentrations accounted for 84% of the variability in the change in IP. Findings demonstrate that a multiple-stressor military training environment induced increases in IP that were associated with alterations in markers of inflammation and with intestinal microbiota composition and metabolism. Associations between IP, the pre-STRESS microbiota, and microbiota metabolites suggest that targeting the intestinal microbiota could provide novel strategies for preserving IP during physiological stress. Military training, a unique model for studying temporal dynamics of intestinal barrier and intestinal microbiota responses to stress, resulted in increased intestinal permeability concomitant with changes in intestinal microbiota composition and metabolism. Prestress intestinal microbiota composition and changes in fecal concentrations of metabolites linked to the microbiota were associated with increased intestinal permeability. Findings suggest that targeting the intestinal microbiota could provide novel strategies for mitigating increases in intestinal permeability during stress.
Highlights d CD14 + monocytes show Marburg virus replication after infection of reservoir bats d Infected bat monocytes and tissues show canonical antiviral response gene induction d Infected bat host response lacks significant induction of immunopathogenic genes d Immunoprotective bat response contrasts starkly to that reported for sick primates
The bidirectional role of gut-brain axis that integrates the gut and central nervous system activities has recently been investigated. We studied "cage-within-cage resident-intruder" all-male model, where subject male mice (C57BL/6J) are exposed to aggressor mice (SJL albino), and gut microbiota-derived metabolites were identified in plasma after 10 days of exposure. We assessed 16S ribosomal RNA gene from fecal samples collected daily from these mice during the 10-day study. Alpha diversity using Chao indices indicated no change in diversity in aggressor-exposed samples. The abundance profile showed the top phyla were Firmicutes and Bacteroidetes, Tenericutes, Verrucomicrobia, Actinobacteria and Proteobacteria, respectively. The phyla Firmicutes and Bacteroidetes are vulnerable to PTSD-eliciting stress and the Firmicutes/Bacteroidetes ratio increases with stress. Principal coordinate analysis showed the control and aggressor-exposed samples cluster separately where samples from early time points (day 1-3) clustered together and were distinct from late time points (day 4-9). The genus-based analysis revealed all control time points clustered together and aggressor-exposed samples had multiple clusters. The decrease in proportion of Firmicutes after aggressor exposure persisted throughout the study. The proportion of Verrucomicrobia immediately decreased and was significantly shifted at most of the later time points. The genus Oscillospira, Lactobacillus, Akkermansia and Anaeroplasma are the top four genera that differed between control and stressor-exposed mice. The data showed immediate effect on microbiome composition during a 10 day time period of stress exposure. Studying the longitudinal effects of a stressor is an important step toward an improved mechanistic understanding of the microbiome dynamics.
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