Karl J Philip, Margolis Lee M, Madslien Elisabeth H, Murphy Nancy E, Castellani John W, Gundersen Yngvar, Hoke Allison V, Levangie Michael W, Kumar Raina, Chakraborty Nabarun, Gautam Aarti, Hammamieh Rasha, Martini Svein, Montain Scott J, Pasiakos Stefan M
Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts;
Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts.
Am J Physiol Gastrointest Liver Physiol. 2017 Jun 1;312(6):G559-G571. doi: 10.1152/ajpgi.00066.2017. Epub 2017 Mar 23.
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.
肠道微生物群对生理应激反应的强度、时间动态和生理影响目前尚不清楚。本研究采用系统生物学方法和多应激源军事训练环境，以确定生理应激对肠道微生物群组成、代谢活性以及肠道通透性（IP）的影响。在为期4天的越野滑雪行军（应激期）中，为73名士兵每天提供三餐，分别添加或不添加蛋白质或碳水化合物补充剂。在应激期之前和期间测量IP。在应激期之前和之后采集血液和粪便样本，以测量炎症、粪便微生物群以及粪便和血浆的整体代谢物谱。在应激期，IP增加了62±57%（平均值±标准差，P<0.001），与饮食组无关，且与炎症增加有关。肠道微生物群反应的特征是α多样性增加，超过50%已鉴定属的相对丰度发生变化，包括以如[未提及具体菌属名称]等优势菌属为代价，增加了非优势菌属的丰度。肠道微生物群组成的变化与应激期后粪便中23%显著改变的代谢物有关。总的来说，应激期前放线菌的相对丰度以及血清白细胞介素-6和粪便半胱氨酸浓度的变化占IP变化变异性的84%。研究结果表明，多应激源军事训练环境导致IP增加，这与炎症标志物的改变以及肠道微生物群组成和代谢有关。IP、应激期前微生物群和微生物群代谢物之间的关联表明，针对肠道微生物群可能为在生理应激期间维持IP提供新策略。军事训练是研究肠道屏障和肠道微生物群对应激反应时间动态的独特模型，导致肠道通透性增加，同时肠道微生物群组成和代谢发生变化。应激期前肠道微生物群组成以及与微生物群相关的粪便代谢物浓度变化与肠道通透性增加有关。研究结果表明，针对肠道微生物群可能为减轻应激期间肠道通透性增加提供新策略。
