Šket Robert, Deutsch Leon, Prevoršek Zala, Mekjavić Igor B, Plavec Janez, Rittweger Joern, Debevec Tadej, Eiken Ola, Stres Blaz
Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
Department of Automation, Biocybernetics and Robotics, Jožef Stefan Institute, Ljubljana, Slovenia.
Front Physiol. 2020 Dec 7;11:532271. doi: 10.3389/fphys.2020.532271. eCollection 2020.
We explored the metabolic makeup of urine in prescreened healthy male participants within the PlanHab experiment. The run-in (5 day) and the following three 21-day interventions [normoxic bedrest (NBR), hypoxic bedrest (HBR), and hypoxic ambulation (HAmb)] were executed in a crossover manner within a controlled laboratory setup (medical oversight, fluid and dietary intakes, microbial bioburden, circadian rhythm, and oxygen level). The inspired O (FO) fraction next to inspired O (PO) partial pressure were 0.209 and 133.1 ± 0.3 mmHg for the NBR variant in contrast to 0.141 ± 0.004 and 90.0 ± 0.4 mmHg (approx. 4,000 m of simulated altitude) for HBR and HAmb interventions, respectively. H-NMR metabolomes were processed using standard quantitative approaches. A consensus of ensemble of multivariate analyses showed that the metabolic makeup at the start of the experiment and at HAmb endpoint differed significantly from the NBR and HBR endpoints. Inactivity alone or combined with hypoxia resulted in a significant reduction of metabolic diversity and increasing number of affected metabolic pathways. Sliding window analysis (3 + 1) unraveled that metabolic changes in the NBR lagged behind those observed in the HBR. These results show that the negative effects of cessation of activity on systemic metabolism are further aggravated by additional hypoxia. The PlanHab HAmb variant that enabled ambulation, maintained vertical posture, and controlled but limited activity levels apparently prevented the development of negative physiological symptoms such as insulin resistance, low-level systemic inflammation, constipation, and depression. This indicates that exercise apparently prevented the negative spiral between the host's metabolism, intestinal environment, microbiome physiology, and proinflammatory immune activities in the host.
我们在“PlanHab”实验中，对预先筛选的健康男性参与者的尿液代谢组成进行了探究。在可控的实验室环境（医疗监督、液体和饮食摄入、微生物生物负荷、昼夜节律及氧气水平）中，以交叉方式进行了导入期（5天）及随后的三个21天干预阶段[常氧卧床休息（NBR）、低氧卧床休息（HBR）和低氧行走（HAmb）]。NBR组的吸入氧（FO）分数及吸入氧（PO）分压分别为0.209和133.1±0.3 mmHg，而HBR和HAmb干预组的相应数值分别为0.141±0.004和90.0±0.4 mmHg（约相当于4000米模拟海拔高度）。采用标准定量方法处理氢核磁共振代谢组数据。多变量分析综合结果显示，实验开始时及HAmb终点时的代谢组成与NBR和HBR终点时存在显著差异。单独的不活动状态或与低氧状态相结合，均导致代谢多样性显著降低以及受影响代谢途径数量增加。滑动窗口分析（3 + 1）表明，NBR中的代谢变化滞后于HBR中观察到的变化。这些结果表明，活动停止对全身代谢的负面影响会因额外的低氧状态而进一步加剧。“PlanHab”的HAmb方案允许行走、保持垂直姿势并控制但限制活动水平，显然预防了诸如胰岛素抵抗、低水平全身炎症、便秘和抑郁等负面生理症状的出现。这表明运动显然阻止了宿主代谢、肠道环境、微生物组生理学和宿主促炎免疫活动之间的负面螺旋式发展。
