The human microbiome in space: parallels between Earth-based dysbiosis, implications for long-duration spaceflight, and possible mitigation strategies.

SUMMARYThe human microbiota encompasses the diverse communities of microorganisms that reside in, on, and around various parts of the human body, such as the skin, nasal passages, and gastrointestinal tract. Although research is ongoing, it is well established that the microbiota exert a substantial influence on the body through the production and modification of metabolites and small molecules. Disruptions in the composition of the microbiota-dysbiosis-have also been linked to various negative health outcomes. As humans embark upon longer-duration space missions, it is important to understand how the conditions of space travel impact the microbiota and, consequently, astronaut health. This article will first characterize the main taxa of the human gut microbiota and their associated metabolites, before discussing potential dysbiosis and negative health consequences. It will also detail the microbial changes observed in astronauts during spaceflight, focusing on gut microbiota composition and pathogenic virulence and survival. Analysis will then turn to how astronaut health may be protected from adverse microbial changes via diet, exercise, and antibiotics before concluding with a discussion of the microbiota of spacecraft and microbial culturing methods in space. The implications of this review are critical, particularly with NASA's ongoing implementation of the Moon to Mars Architecture, which will include weeks or months of living in space and new habitats.

Changes in the astronaut serum proteome during prolonged spaceflight.

The molecular mechanisms associated with spaceflight-induced biological adaptations that may affect many healthy tissue functions remain poorly understood. In this study, we analyzed temporal changes in the serum proteome of six astronauts during prolonged spaceflight missions using quantitative comprehensive proteome analysis performed with the data-independent acquisition method of mass spectrometry (DIA-MS). All six astronauts participated in a spaceflight mission for approximately 6 months and showed a decreasing trend in T-scores at almost all sites where dual-energy X-ray absorptiometry scans were performed. DIA-MS successfully identified 624 nonredundant proteins in sera and further quantitative analysis for each sampling point provided information on serum protein profiles closely related to several time points before (pre-), during (in-), and after (post-) spaceflight. Changes in serum protein levels between spaceflight and on the ground suggest that abnormalities in bone metabolism are induced in astronauts during spaceflight. Furthermore, changes in the proteomic profile occurring during spaceflight suggest that serum levels of bone metabolism-related proteins, namely ALPL, COL1A1, SPP1, and POSTN, could serve as highly responsive indicators of bone metabolism status in spaceflight missions. This study will allow us to accelerate research to improve our understanding of the molecular mechanisms of biological adaptations associated with prolonged spaceflight.

Plasticity of the heart in response to changes in physical activity.

The human heart is very adaptable, with chamber size, wall thickness and ventricular stiffness all modified by periods of inactivity or exercise training. Herein, we summarize the cardiac adaptations induced by changes in physical activity, ranging from bed rest and spaceflight to endurance exercise training, while also highlighting how the ageing process (a long-term model of inactivity) affects cardiac plasticity. Severe inactivity during bed rest or spaceflight leads to cardiac atrophy and ventriculo-vascular stiffening. Conversely, endurance training induces eccentric hypertrophy and enhances ventricular compliance, and can be used as an effective countermeasure to prevent adverse cardiac changes during prolonged periods of bed rest or spaceflight. With sedentary ageing, the heart undergoes concentric remodelling and irreversibly stiffens at advanced age. Specifically, older adults who initiate endurance training later in life are unable to improve ventricular compliance and diastolic function, suggesting reduced cardiac plasticity with advanced age; however, lifelong exercise training prevents age-associated cardiac remodelling and maintains cardiac compliance of older adults at a level similar to those of younger healthy individuals. Nevertheless, there are still many knowledge gaps related to cardiac remodelling and changes in cardiac function induced by bed rest, exercise training and spaceflight, as well as how these different stimuli may interact with advancing age. Future studies should focus on understanding what factors (sex, age, heritability, etc.) may influence the heart's responsiveness to training or deconditioning, as well as understanding the long-term cardiac consequences of spaceflight beyond low-Earth orbit with the added stimulus of galactic cosmic radiation.

An experimentally informed computational model of neurovestibular adaptation to altered gravity.

Transitions to altered gravity environments result in acute sensorimotor impairment for astronauts, leading to serious mission and safety risks in the crucial first moments in a new setting. Our understanding of the time course and severity of impairment in the early stages of adaptation remains limited and confounded by unmonitored head movements, which are likely to impact the rate of adaptation. Here, we aimed to address this gap by using a human centrifuge to simulate the first hour of hypergravity (1.5g) exposure and the subsequent 1g readaptation period, with precisely controlled head tilt activity. We quantified head tilt overestimation via subjective visual vertical and found ∼30% tilt overestimation that did not decrease over the course of 1 h of exposure to the simulated gravity environment. These findings extended the floor of the vestibular adaptation window (with controlled vestibular cueing) to 1 h of exposure to altered gravity. We then used the empirical data to inform a computational model of neurovestibular adaptation to changes in the magnitude of gravity, which can offer insight into the adaptation process and, with further tuning, can be used to predict the temporal dynamics of vestibular-mediated misperceptions in altered gravity.

Blood flow restriction: The acute effects of body tilting and reduced gravity analogues on limb occlusion pressure.

Blood flow restriction (BFR) has been identified as a potential countermeasure to mitigate physiological deconditioning during spaceflight. Guidelines recommend that tourniquet pressure be prescribed relative to limb occlusion pressure (LOP); however, it is unclear whether body tilting or reduced gravity analogues influence LOP. We examined LOP at the leg and arm during supine bedrest and bodyweight suspension (BWS) at 6° head-down tilt (HDT), horizontal (0°), and 9.5° head-up tilt (HUT) positions. Twenty-seven adults (age, 26 ± 5 years; height, 1.75 ± 0.08 m; body mass, 73 ± 12 kg) completed all tilts during bedrest. A subgroup (n = 15) additionally completed the tilts during BWS. In each position, LOP was measured twice in the leg and arm using the Delfi Personalized Tourniquet System after 5 min of rest and again after a further 5 min. The LOP at the leg increased significantly from 6° HDT to 9.5° HUT in bedrest and BWS by 9-15 mmHg (Cohen's d = 0.7-1.0). Leg LOP was significantly higher during BWS at horizontal and 9.5° HUT postures relative to the same angles during bedrest by 8 mmHg (Cohen's d = 0.6). Arm LOP remained unchanged between body tilts and analogues. Intraclass correlation coefficients for LOP measurements taken after an initial and subsequent 5 min rest period in all conditions ranged between 0.91-0.95 (leg) and 0.83-0.96 (arm). It is advised that LOP be measured before the application of a vascular occlusion in the same body tilt/setting to which it is applied to minimize discrepancies between the actual and prescribed tourniquet pressure.

Leveraging Spaceflight to Advance Cardiovascular Research on Earth.

The direct (eg, radiation, microgravity) and indirect (eg, lifestyle perturbations) effects of spaceflight extend across multiple systems resulting in whole-organism cardiovascular deconditioning. For over 50 years, National Aeronautics and Space Administration has continually enhanced a countermeasures program designed to characterize and offset the adverse cardiovascular consequences of spaceflight. In this review, we provide a historical overview of research evaluating the effects of spaceflight on cardiovascular health in astronauts and outline mechanisms underpinning spaceflight-related cardiovascular alterations. We also discuss how spaceflight could be leveraged for aging, industry, and model systems such as human induced pluripotent stem cell-derived cardiomyocytes, organoid, and organ-on-a-chip technologies. Finally, we outline the increasing opportunities for scientists and clinicians to engage in cardiovascular research in space and on Earth.

Smart Task Assistance in Mixed Reality for Astronauts.

Mixed reality (MR) registers virtual information and real objects and is an effective way to supplement astronaut training. Spatial anchors are generally used to perform virtual-real fusion in static scenes but cannot handle movable objects. To address this issue, we propose a smart task assistance method based on object detection and point cloud alignment. Specifically, both fixed and movable objects are detected automatically. In parallel, poses are estimated with no dependence on preset spatial position information. Firstly, YOLOv5s is used to detect the object and segment the point cloud of the corresponding structure, called the partial point cloud. Then, an iterative closest point (ICP) algorithm between the partial point cloud and the template point cloud is used to calculate the object's pose and execute the virtual-real fusion. The results demonstrate that the proposed method achieves automatic pose estimation for both fixed and movable objects without background information and preset spatial anchors. Most volunteers reported that our approach was practical, and it thus expands the application of astronaut training.

Rapid Dual-Task Decrements After a Brief Period of Manual Tracking in Simulated Weightlessness by Water Submersion.

OBJECTIVE: Investigating dual-task (DT) performance during simulated weightlessness by water submersion, using a manual tracking and a choice reaction task. In contrast to previous work, we focus on performance changes over time. BACKGROUND: Previous research showed motor tracking and choice reaction impairments under DT and single-task (ST) conditions in shallow water submersion. Recent research analyzed performance as average across task time, neglecting potential time-related changes or fluctuations of task-performance. METHOD: An unstable tracking and a choice reaction task was performed for one minute under ST and DT conditions in 5 m water submersion and on dry land in 43 participants. Tracking and choice reaction time performance for both tasks were analyzed in blocks of 10 seconds. RESULTS: Tracking performance deteriorated underwater compared to dry land conditions during the second half while performing one minute in DT conditions. Choice reaction time increased underwater as well, but independent of task time and type. CONCLUSION: Tracking error increased over time when performing unstable tracking and choice reaction together. Potentially, physiological and psychological alterations under shallow submersion further strain the human system during DT operations, exceeding available recourse capacities such that DT performance deteriorated over time. APPLICATION: Humans operating in simulated weightlessness underwater should be aware of substantial performance declines that can occur within a short amount of time during DT situations that include continuous tracking.

The Next Giant Leap for Space Human Factors: The Opportunities.

OBJECTIVE: Propose areas of future space human factors research. BACKGROUND: Deep space, long-duration human spaceflight missions to the Moon and Mars still require advances in space human factors research. Key drivers relate to astronauts living and working in isolation, new novel technologies required to accomplish exploration missions, and the longer durations of these. RESULTS: Three areas of research are proposed for methods and techniques: (1) to enable more autonomous astronauts; (2) to monitor crew and improve ground team situation awareness; and (3) to detect and support changes in long-duration team coordination. CONCLUSIONS: Future human exploration missions will benefit from advances in space human factors research. APPLICATION: Human factors researchers can contribute to human spaceflight by prioritizing these research topics.

A Mission to Mars: Prediction of GCR Doses and Comparison with Astronaut Dose Limits.

Long-term human space missions such as a future journey to Mars could be characterized by several hazards, among which radiation is one the highest-priority problems for astronaut health. In this work, exploiting a pre-existing interface between the BIANCA biophysical model and the FLUKA Monte Carlo transport code, a study was performed to calculate astronaut absorbed doses and equivalent doses following GCR exposure under different shielding conditions. More specifically, the interface with BIANCA allowed us to calculate both the RBE for cell survival, which is related to non-cancer effects, and that for chromosome aberrations, related to the induction of stochastic effects, including cancer. The results were then compared with cancer and non-cancer astronaut dose limits. Concerning the stochastic effects, the equivalent doses calculated by multiplying the absorbed dose by the RBE for chromosome aberrations ("high-dose method") were similar to those calculated using the Q-values recommended by ICRP. For a 650-day mission at solar minimum (representative of a possible Mars mission scenario), the obtained values are always lower than the career limit recommended by ICRP (1 Sv), but higher than the limit of 600 mSv recently adopted by NASA. The comparison with the JAXA limits is more complex, since they are age and sex dependent. Concerning the deterministic limits, even for a 650-day mission at solar minimum, the values obtained by multiplying the absorbed dose by the RBE for cell survival are largely below the limits established by the various space agencies. Following this work, BIANCA, interfaced with an MC transport code such as FLUKA, can now predict RBE values for cell death and chromosome aberrations following GCR exposure. More generally, both at solar minimum and at solar maximum, shielding of 10 g/cm2 Al seems to be a better choice than 20 g/cm2 for astronaut protection against GCR.

Nutrition as Fuel for Human Spaceflight.

History books are rife with examples of the role of nutrition in determining either the success or the failure of human exploration on Earth. With planetary exploration in our future, it is imperative that we understand the role of nutrition in optimizing health before humans can safely take the next giant leaps in space exploration.

Sixty days of head-down tilt bed rest with or without artificial gravity do not affect the neuromuscular secretome.

Artificial gravity is a potential countermeasure to attenuate effects of weightlessness during long-term spaceflight, including losses of muscle mass and function, possibly to some extent attributable to disturbed neuromuscular interaction. The 60-day AGBRESA bed-rest study was conducted with 24 participants (16 men, 8 women; 33 ± 9 years; 175 ± 9 cm; 74 ± 10 kg; 8 control group, 8 continuous (cAG) and 8 intermittent (iAG) centrifugation) to assess the impact of bed rest with or without daily 30-min continuous/intermittent centrifugation with 1G at the centre of mass. Fasting blood samples were collected before and on day 6, 20, 40 and 57 during 6° head-down tilt bed rest. Concentrations of circulating markers of muscle wasting (GDF-8/myostatin; slow skeletal muscle troponin T; prostaglandin E2), neurotrophic factors (BDNF; GDNF) and C-terminal Agrin Fragment (CAF) were determined by ELISAs. Creatine kinase activity was assessed by colorimetric enzyme assay. Repeated-measures ANOVAs were conducted with TIME as within-subject, and INTERVENTION and SEX as between-subject factors. The analyses revealed no significant effect of bed rest or sex on any of the parameters. Continuous or intermittent artificial gravity is a safe intervention that does not have a negative impact of the neuromuscular secretome.

Cervical spine and muscle adaptation after spaceflight and relationship to herniation risk: protocol from 'Cervical in Space' trial.

BACKGROUND: Astronauts have a higher risk of cervical intervertebral disc herniation. Several mechanisms have been attributed as causative factors for this increased risk. However, most of the previous studies have examined potential causal factors for lumbar intervertebral disc herniation only. Hence, we aim to conduct a study to identify the various changes in the cervical spine that lead to an increased risk of cervical disc herniation after spaceflight. METHODS: A cohort study with astronauts will be conducted. The data collection will involve four main components: a) Magnetic resonance imaging (MRI); b) cervical 3D kinematics; c) an Integrated Protocol consisting of maximal and submaximal voluntary contractions of the neck muscles, endurance testing of the neck muscles, neck muscle fatigue testing and questionnaires; and d) dual energy X-ray absorptiometry (DXA) examination. Measurements will be conducted at several time points before and after astronauts visit the International Space Station. The main outcomes of interest are adaptations in the cervical discs, muscles and bones. DISCUSSION: Astronauts are at higher risk of cervical disc herniation, but contributing factors remain unclear. The results of this study will inform future preventive measures for astronauts and will also contribute to the understanding of intervertebral disc herniation risk in the cervical spine for people on Earth. In addition, we anticipate deeper insight into the aetiology of neck pain with this research project. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00026777. Registered on 08 October 2021.

The thrombotic risk of spaceflight: has a serious problem been overlooked for more than half of a century?

The first ever venous thrombotic condition associated with spaceflight, an internal jugular vein thrombus requiring anticoagulation, has recently been reported. Systematic investigation of space travel-associated thrombotic risk has not been conducted. Cellular, animal, and human studies performed in ground-based models and in actual weightlessness revealed influences of weightlessness and gravity on the blood coagulation system. However, human study populations were small and limited to highly selected participants. Evidence in individuals with medical conditions and older persons is lacking. Evidence for thrombotic risk in spaceflight is unsatisfactory. This issue deserves further study in heterogeneous, high risk populations to find prevention strategies and to enable safe governmental and touristic human spaceflight.

Extraterrestrial Gynecology: Could Spaceflight Increase the Risk of Developing Cancer in Female Astronauts? An Updated Review.

Outer space is an extremely hostile environment for human life, with ionizing radiation from galactic cosmic rays and microgravity posing the most significant hazards to the health of astronauts. Spaceflight has also been shown to have an impact on established cancer hallmarks, possibly increasing carcinogenic risk. Terrestrially, women have a higher incidence of radiation-induced cancers, largely driven by lung, thyroid, breast, and ovarian cancers, and therefore, historically, they have been permitted to spend significantly less time in space than men. In the present review, we focus on the effects of microgravity and radiation on the female reproductive system, particularly gynecological cancer. The aim is to provide a summary of the research that has been carried out related to the risk of gynecological cancer, highlighting what further studies are needed to pave the way for safer exploration class missions, as well as postflight screening and management of women astronauts following long-duration spaceflight.

Acceptability of the Cognition Test Battery in Astronaut and Astronaut-Surrogate Populations.

BACKGROUND: Sustained high levels of astronaut cognitive performance are a prerequisite for mission success. A neuropsychological battery of 10 brief cognitive tests (Cognition) covering a range of cognitive domains was specifically developed for high performing astronauts to objectively assess cognitive performance. Extended mission durations require repeated cognitive testing and thus high acceptability of the Cognition software to the astronaut population. The aim of this qualitative study was to evaluate acceptability of Cognition to astronauts and astronaut surrogate populations. METHODS: Cognition was administered repeatedly to N=87 subjects (mean age ±SD 35.1 ±8.7 years, 52.8% male) on a laptop or iPad across five individual studies on the International Space Station or in space analog environments on Earth. Following completion of each study, participants were interviewed regarding their experience using Cognition in a semi-structured debrief. Participant comments were analyzed using a qualitative conventional content analysis approach. RESULTS: The majority of participants' comments (86.1%) were coded as positive or neutral in valence, with most positive comments relating to software usability, engagement, and overall design. Among the 10 Cognition tests, subjects liked the Visual Object Learning Test most (28 likes, 32.2% of participants), while the Emotion Recognition Test was liked least (44 dislikes, 50.6% of participants). Some subjects (36.8%) were frustrated with the level of difficulty of some of the 10 Cognition tests, especially during early administrations, which was by design to avoid ceiling effects in repeated administrations of high-performers. Technical difficulties were rare (20.7% of participants), and most often observed in environments with restricted internet access. Most participants (82.3% of those who commented) liked the feedback provided by Cognition after each test, which includes a graph showing performance history. CONCLUSION: Cognition was found to be acceptable to astronaut and astronaut-surrogate populations across a variety of settings and mission durations. Participant feedback provided was used to further improve Cognition and increase its acceptability during sustained space missions.

Identification of fungi isolated from astronaut nasal and pharyngeal smears and saliva.

As part of a series of studies regarding the microbiota in manned space environments, we isolated the fungal strains from nasal and pharyngeal smears and saliva of 21 astronauts preflight, in-flight, and postflight. On the ground, 120 strains from 43 genera of environmental fungi were isolated from the astronauts. The dominant fungal genera were Cladosporium, Penicillium, and Aspergillus. Only 18 strains from four genera were isolated from the astronauts inside the International Space Station. These fungi are currently thought to be harmless, but regular screening and cleaning are necessary to prevent fungus-related health disorders.

Daily 30-min exposure to artificial gravity during 60 days of bed rest does not maintain aerobic exercise capacity but mitigates some deteriorations of muscle function: results from the AGBRESA RCT.

PURPOSE: Spaceflight impairs physical capacity. Here we assessed the protective effect of artificial gravity (AG) on aerobic exercise capacity and muscle function during bed rest, a spaceflight analogue. METHODS: 24 participants (33 ± 9 years, 175 ± 9 cm, 74 ± 10 kg, 8 women) were randomly allocated to one of three groups: continuous AG (cAG), intermittent AG (iAG) or control (CTRL). All participants were subjected to 60 days of six-degree head-down tilt bed rest, and subjects of the intervention groups completed 30 min of centrifugation per day: cAG continuously and iAG for 6 × 5 min, with an acceleration of 1g at the center of mass. Physical capacity was assessed before and after bed rest via maximal voluntary contractions, cycling spiroergometry, and countermovement jumps. RESULTS: AG had no significant effect on aerobic exercise capacity, flexor muscle function and isometric knee extension strength or rate of force development (RFD). However, AG mitigated the effects of bed rest on jumping power (group * time interaction of the rmANOVA p < 0.001; iAG - 25%, cAG - 26%, CTRL - 33%), plantar flexion strength (group * time p = 0.003; iAG - 35%, cAG - 31%, CTRL - 48%) and plantar flexion RFD (group * time p = 0.020; iAG - 28%, cAG - 12%, CTRL - 40%). Women showed more pronounced losses than men in jumping power (p < 0.001) and knee extension strength (p = 0.010). CONCLUSION: The AG protocols were not suitable to maintain aerobic exercise capacity, probably due to the very low cardiorespiratory demand of this intervention. However, they mitigated some losses in muscle function, potentially due to the low-intensity muscle contractions during centrifugation used to avoid presyncope.

Effects of Spaceflight on Human Skin.

During both short- and long-duration spaceflight, several health problems can occur, including those of the skin. Astronauts in space and after returning to earth experience erythematous, burning, itchy, dry, sensitive, and thinning skin. Other skin problems, such as infections, abrasions, lacerations, delayed wound healing, and accelerated skin aging, are also common. Human skin is an ecosystem composed of a wide range of habitats for bacteria, fungi, and viruses called microbiome, which not only show a strong skin site-specific preference but also serve as microbial fingerprints that are highly unique to individuals. These human skin-associated microorganisms make a substantial contribution to the microbial ecosystems that inhabit the closed environments in space. On the other hand, human skin microbiome is also subject to change during spaceflight, which may lead to skin infections or the flare up of skin diseases. This review highlights some of the interactions between the space environment and the skin.

Modular Robotic Limbs for Astronaut Activities Assistance.

In order to meet the assist requirements of extravehicular activity (EVA) for astronauts, such as moving outside the international space station (ISS) or performing on-orbit tasks by a single astronaut, this paper proposes an astronaut robotic limbs system (AstroLimbs) for extravehicular activities assistance. This system has two robotic limbs that can be fixed on the backpack of the astronaut. Each limb is composed of several basic module units with identical structure and function, which makes it modularized and reconfigurable. The robotic limbs can work as extra arms of the astronaut to assist them outside the space station cabin. In this paper, the robotic limbs are designed and developed. The reinforcement learning method is introduced to achieve autonomous motion planning capacity for the robot, which makes the robot intelligent enough to assist the astronaut in unstructured environment. In the meantime, the movement of the robot is also planned to make it move smoothly. The structure scene of the ISS for extravehicular activities is modeled in a simulation environment, which verified the effectiveness of the proposed method.