Systems View of Deconditioning During Spaceflight Simulation in the PlanHab Project: The Departure of Urine 1 H-NMR Metabolomes From Healthy State in Young Males Subjected to Bedrest Inactivity and Hypoxia

Robert Šket; Leon Deutsch; Zala Prevoršek; Igor B Mekjavić; Janez Plavec; Joern Rittweger; Tadej Debevec; Ola Eiken; Blaz Stres

doi:10.3389/fphys.2020.532271

Systems View of Deconditioning During Spaceflight Simulation in the PlanHab Project: The Departure of Urine ¹ H-NMR Metabolomes From Healthy State in Young Males Subjected to Bedrest Inactivity and Hypoxia

Front Physiol. 2020 Dec 7:11:532271. doi: 10.3389/fphys.2020.532271. eCollection 2020.

Authors

Robert Šket¹, Leon Deutsch¹, Zala Prevoršek¹, Igor B Mekjavić², Janez Plavec³, Joern Rittweger⁴, Tadej Debevec^{2

5}, Ola Eiken⁶, Blaz Stres^{1

2

7

8

9}

Affiliations

¹ Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
² Department of Automation, Biocybernetics and Robotics, Jožef Stefan Institute, Ljubljana, Slovenia.
³ National Institute of Chemistry, NMR Center, Ljubljana, Slovenia.
⁴ German Aerospace Center, Institute of Aerospace Medicine, Muscle and Bone Metabolism, Köln, Germany.
⁵ Faculty of Sports, University of Ljubljana, Ljubljana, Slovenia.
⁶ Department of Environmental Physiology, Swedish Aerospace Physiology Centre, KTH Royal Institute of Technology, Stockholm, Sweden.
⁷ Faculty of Civil and Geodetic Engineering, Institute of Sanitary Engineering, University of Ljubljana, Ljubljana, Slovenia.
⁸ Laboratory for Clinical Toxicology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
⁹ Department of Microbiology, University of Innsbruck, Innsbruck, Austria.

Abstract

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 O₂ (F_iO₂) fraction next to inspired O₂ (P_iO₂) 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. ¹H-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.

Keywords: NMR; deconditioning; inactivity; inflammation; interplanetary travel; medicine; metabolome; urine.