Safety protocols, precautions, and countermeasures aboard the International Space Station (ISS) to prevent ocular injury.

The International Space Station (ISS) is a $100 billion epicenter of human activity in the vacuum of space, displaying mankind's collective endeavor to explore the cosmic frontier. Even within the marvels of technological sophistication aboard the ISS, the human eye remains a highly vulnerable structure. In the absence of multiple layers of protection and risk assessments, crewmembers would face a substantial increase in vulnerability to ocular injury. Aside from stringent preflight screening criteria for astronauts, the ISS is equipped with ophthalmic medications, environmental control and life support systems (e.g., humidity regulation, carbon dioxide removal, pressurized device regulators), and radiation protection to reduce ocular injury. Moreover, additional countermeasures are currently being developed to mitigate the effects of spaceflight-associated neuro-ocular syndrome (SANS) and lunar dust toxicity for the Artemis Program missions. The success of future endeavors hinges not only on continued technological innovation, but also respecting the intricate interplay between human physiology and the extraterrestrial environments. Establishing habitations on the Moon and Mars, as well as NASA's Gateway Program (humanity's first space station around the Moon), will introduce a new set of challenges, underscoring the necessity for continuous insights into ocular health in space. We discuss the safety protocols, precautions, and countermeasures implemented on the ISS to prevent ocular injury - an aspect often overshadowed by the grandeur of space exploration.

The Astrobiological Potential of the Uranian Moon System.

The 2023-2032 Planetary Science and Astrobiology Decadal Survey prioritized the Uranus Orbiter and Probe (UOP) mission concept as the next priority flagship mission. The UOP concept includes scientific studies of the Uranian moon system. Although the Uranian moons differ greatly from the ocean worlds in the Jovian and Saturnian systems, the emerging hypothesis is that some of them could at least sustain thin, potentially concentrated, oceans. Herein, we make a case that these moons are important and interesting targets of astrobiological research. Studying these worlds would provide critical astrobiological data related to their habitability, including origin, evolution, and potential death, as well as the formation and evolution of ocean worlds more broadly. There is a strong need for research that connects astrobiology to modeling and experimentation to better characterize the possible conditions of these worlds, and this will be critical in formulating and maximizing the potential science that could be done by a Uranus flagship mission.

Microbiology of human spaceflight: microbial responses to mechanical forces that impact health and habitat sustainability.

SUMMARYUnderstanding the dynamic adaptive plasticity of microorganisms has been advanced by studying their responses to extreme environments. Spaceflight research platforms provide a unique opportunity to study microbial characteristics in new extreme adaptational modes, including sustained exposure to reduced forces of gravity and associated low fluid shear force conditions. Under these conditions, unexpected microbial responses occur, including alterations in virulence, antibiotic and stress resistance, biofilm formation, metabolism, motility, and gene expression, which are not observed using conventional experimental approaches. Here, we review biological and physical mechanisms that regulate microbial responses to spaceflight and spaceflight analog environments from both the microbe and host-microbe perspective that are relevant to human health and habitat sustainability. We highlight instrumentation and technology used in spaceflight microbiology experiments, their limitations, and advances necessary to enable next-generation research. As spaceflight experiments are relatively rare, we discuss ground-based analogs that mimic aspects of microbial responses to reduced gravity in spaceflight, including those that reduce mechanical forces of fluid flow over cell surfaces which also simulate conditions encountered by microorganisms during their terrestrial lifecycles. As spaceflight mission durations increase with traditional astronauts and commercial space programs send civilian crews with underlying health conditions, microorganisms will continue to play increasingly critical roles in health and habitat sustainability, thus defining a new dimension of occupational health. The ability of microorganisms to adapt, survive, and evolve in the spaceflight environment is important for future human space endeavors and provides opportunities for innovative biological and technological advances to benefit life on Earth.

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.

Cardiovascular effects of long-duration space flight.

Introduction: Early studies exploring the physiological effects of space travel have indicated the body's capacity for reversible adaptation. However, the impact of long-duration spaceflight, exceeding 6 months, presents more intricate challenges. Effects on the Cardiovascular CV System: Extended exposure to microgravity and radiation profoundly affects the CV system. Notable phenomena include fluid shifts toward the head and modified arterial pressure. These changes disrupt blood pressure regulation and elevate cardiac output. Additionally, the loss of venous compression leads to a reduction in central venous pressure. Fluid and Plasma Volume Changes: The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%-15% decline in plasma volume. Cardiac Muscle and Hematocrit Variations: Intriguingly, despite potential increases in cardiac workload, cardiac muscle atrophy and perplexing variations in hematocrit levels have been observed. The mechanism underlying atrophy appears to involve a shift in protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated mechanisms. Arrhythmias and QT Interval Prolongation: Instances of arrhythmias have been recurrently documented, although generally nonlethal, in both Russian and American space missions. Long-duration spaceflight has been associated with the prolongation of the QT interval, particularly in extended missions. Radiation Effects: Exposure of the heart to the proton and heavy ion radiation pervasive in deep space contributes to coronary artery degeneration, augmented aortic stiffness, and carotid intima thickening through collagen-mediated processes. Moreover, it accelerates the onset of atherosclerosis and triggers proinflammatory responses. Reentry and Postflight Challenges: Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. Conclusion: Consequently, careful monitoring of these cardiac risks is imperative for forthcoming missions. While early studies illuminate the adaptability of the body to space travel's challenges, the intricacies of long-duration missions and their effects on the CV system necessitate continued investigation and vigilance to ensure astronaut health and mission success.

Effects of weightlessness on the cardiovascular system: a systematic review and meta-analysis.

Background: The microgravity environment has a direct impact on the cardiovascular system due to the fluid shift and weightlessness that results in cardiac dysfunction, vascular remodeling, and altered Cardiovascular autonomic modulation (CAM), deconditioning and poor performance on space activities, ultimately endangering the health of astronauts. Objective: This study aimed to identify the acute and chronic effects of microgravity and Earth analogues on cardiovascular anatomy and function and CAM. Methods: CINAHL, Cochrane Library, Scopus, Science Direct, PubMed, and Web of Science databases were searched. Outcomes were grouped into cardiovascular anatomic, functional, and autonomic alterations, and vascular remodeling. Studies were categorized as Spaceflight (SF), Chronic Simulation (CS), or Acute Simulation (AS) based on the weightlessness conditions. Meta-analysis was performed for the most frequent outcomes. Weightlessness and control groups were compared. Results: 62 articles were included with a total of 963 participants involved. The meta-analysis showed that heart rate increased in SF [Mean difference (MD) = 3.44; p = 0.01] and in CS (MD = 4.98; p < 0.0001), whereas cardiac output and stroke volume decreased in CS (MD = -0.49; p = 0.03; and MD = -12.95; p < 0.0001, respectively), and systolic arterial pressure decreased in AS (MD = -5.20; p = 0.03). According to the qualitative synthesis, jugular vein cross-sectional area (CSA) and volume were greater in all conditions, and SF had increased carotid artery CSA. Heart rate variability and baroreflex sensitivity, in general, decreased in SF and CS, whereas both increased in AS. Conclusion: This review indicates that weightlessness impairs the health of astronauts during and after spaceflight, similarly to the effects of aging and immobility, potentially increasing the risk of cardiovascular diseases. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020215515.

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.

Self-Generated Lower Body Negative Pressure Exercise: A Low Power Countermeasure for Acute Space Missions.

Microgravity in spaceflight produces headward fluid shifts which probably contribute to Spaceflight-Associated Neuro-Ocular Syndrome (SANS). Developing new methods to mitigate these shifts is crucial for preventing SANS. One possible strategy is the use of self-generated lower body negative pressure (LBNP). This study evaluates biological or physiological effects induced by bed rest to simulate adaptations to microgravity. Participants were tested during powered LBNP and dynamic self-generated (SELF) LBNP at 25 mmHg for 15 min. The results were compared to the physiologic responses observed in seated upright and supine positions without LBNP, which served as controls for normal gravitational effects on fluid dynamics. Eleven participants' (five male, six female) heart rates, blood pressures, and cross-sectional areas (CSA) of left and right internal jugular veins (IJV) were monitored. Self-generated LBNP, which requires mild to moderate physical activity, significantly elevated heart rate and blood pressure (p < 0.01). Self-generated LBNP also significantly reduced right IJV CSA compared to supine position (p = 0.005), though changes on the left side were not significant (p = 0.365). While the effects of SELF and traditional LBNP on IJV CSA were largely similar, traditional LBNP significantly reduced IJV CSA on both sides. Given its low mass, volume, and power requirements, SELF LBNP is a promising countermeasure against SANS. Results from this study warrant longer-term studies of SELF LBNP under simulated spaceflight conditions.

Integrated analysis of miRNAome and transcriptome reveals that microgravity induces the alterations of critical functional gene modules via the regulation of miRNAs in short-term space-flown C. elegans.

Microgravity, as a unique hazardous factor encountered in space, can induce a series of harmful effects on living organisms. The impact of microgravity on the pivotal functional gene modules stemming from gene enrichment analysis via the regulation of miRNAs is not fully illustrated. To explore the microgravity-induced alterations in critical functional gene modules via the regulation of miRNAs, in the present study, we proposed a novel bioinformatics algorithm for the integrated analysis of miRNAome and transcriptome from short-term space-flown C. elegans. The samples of C. elegans were exposed to two space conditions, namely spaceflight (SF) and spaceflight control (SC) onboard the International Space Station for 4 days. Additionally, the samples of ground control (GC) were included for comparative analysis. Using the present algorithm, we constructed regulatory networks of functional gene modules annotated from differentially expressed genes (DEGs) and their associated regulatory differentially expressed miRNAs (DEmiRNAs). The results showed that functional gene modules of molting cycle, defense response, fatty acid metabolism, lysosome, and longevity regulating pathway were facilitated by 25 down-regulated DEmiRNAs (e.g., cel-miR-792, cel-miR-65, cel-miR-70, cel-lsy-6, cel-miR-796, etc.) in the SC vs. GC groups, whereas these modules were inhibited by 13 up-regulated DEmiRNAs (e.g., cel-miR-74, cel-miR-229, cel-miR-70, cel-miR-249, cel-miR-85, etc.) in the SF vs. GC groups. These findings indicated that microgravity could significantly alter gene expression patterns and their associated functional gene modules in short-term space-flown C. elegans. Additionally, we identified 34 miRNAs as post-transcriptional regulators that modulated these functional gene modules under microgravity conditions. Through the experimental verification, our results demonstrated that microgravity could induce the down-regulation of five critical functional gene modules (i.e., molting cycle, defense response, fatty acid metabolism, lysosome, and longevity regulating pathways) via the regulation of miRNAs in short-term space-flown C. elegans.

Imaging in spaceflight associated neuro-ocular syndrome (SANS): Current technology and future directions in modalities.

With plans for future long-duration crewed exploration, NASA has identified several high priority potential health risks to astronauts in space. One such risk is a collection of neurologic and ophthalmic findings termed spaceflight associated neuro-ocular syndrome (SANS). The findings of SANS include optic disc edema, globe flattening, retinal nerve fiber layer thickening, chorioretinal folds, hyperopic shifts, and cotton-wool spots. The cause of SANS was initially thought to be a cephalad fluid shift in microgravity leading to increased intracranial pressure, venous stasis and impaired CSF outflow, but the precise etiology of SANS remains ill defined. Recent studies have explored multiple possible pathogenic mechanisms for SANS including genetic and hormonal factors; a cephalad shift of fluid into the orbit and brain in microgravity; and disruption to the brain glymphatic system. Orbital, ocular, and cranial imaging, both on Earth and in space has been critical in the diagnosis and monitoring of SANS (e.g., fundus photography, optical coherence tomography (OCT), magnetic resonance imaging (MRI), and orbital/cranial ultrasound). In addition, we highlight near-infrared spectroscopy and diffusion tensor imaging, two newer modalities with potential use in future studies of SANS. In this manuscript we provide a review of these modalities, outline their current and potential use in space and on Earth, and review the reported major imaging findings in SANS.

Neurostimulation as a technology countermeasure for dry eye syndrome in astronauts.

Dry eye syndrome (DES) poses a significant challenge for astronauts during space missions, with reports indicating up to 30% of International Space Station (ISS) crew members. The microgravity environment of space alters fluid dynamics, affecting distribution of fluids on the surface of the eye as well as inducing cephalad fluid shifts that can alter tear drainage. Chronic and persistent DES not only impairs visual function, but also compromises the removal of debris, a heightened risk for corneal abrasions in the microgravity environment. Despite the availability of artificial tears on the ISS, the efficacy is challenged by altered fluid dynamics within the bottle and risks of contamination, thereby exacerbating the potential for corneal abrasions. In light of these challenges, there is a pressing need for innovative approaches to address DES in astronauts. Neurostimulation has emerged as a promising technology countermeasure for DES in spaceflight. By leveraging electrical signals to modulate neural function, neurostimulation offers a novel therapeutic avenue for managing DES symptoms. In this paper, we will explore the risk factors and current treatment modalities for DES, highlighting the limitations of existing approaches. Furthermore, we will delve into the novelty and potential of neurostimulation as a countermeasure for DES in future long-duration missions, including those to the Moon and Mars.

Lower body negative pressure as a research tool and countermeasure for the physiological effects of spaceflight: A comprehensive review.

Lower Body Negative Pressure (LBNP) redistributes blood from the upper body to the lower body. LBNP may prove to be a countermeasure for the multifaceted physiological changes endured by astronauts during spaceflight related to cephalad fluid shift. Over more than five decades, beginning with the era of Skylab, advancements in LBNP technology have expanded our understanding of neurological, ophthalmological, cardiovascular, and musculoskeletal adaptations in space, with particular emphasis on mitigating issues such as bone loss. To date however, no comprehensive review has been conducted that chronicles the evolution of this technology or elucidates the broad-spectrum potential of LBNP in managing the diverse physiological challenges encountered in the microgravity environment. Our study takes a chronological perspective, systematically reviewing the historical development and application of LBNP technology in relation to the various pathophysiological impacts of spaceflight. The primary objective is to illustrate how this technology, as it has evolved, offers an increasingly sophisticated lens through which to interpret the systemic effects of space travel on human physiology. We contend that the insights gained from LBNP studies can significantly aid in formulating targeted and effective countermeasures to ensure the health and safety of astronauts. Ultimately, this paper aspires to promote a more cohesive understanding of the broad applicability of LBNP as a countermeasure against multiple bodily effects of space travel, thereby contributing to a safer and more scientifically informed approach to human space exploration.

Impedance threshold device as a countermeasure for spaceflight associated neuro-ocular syndrome (SANS): Mitigating mechanisms in proposed pathophysiology.

Long-duration spaceflight (LDSF) is associated with unique hazards and linked with numerous human health risks including Spaceflight Associated Neuro-ocular Syndrome (SANS). The proposed mechanisms for SANS include microgravity induced cephalad fluid shift and increased Intracranial Pressure (ICP). SANS is a disorder seen only after LDSF and has no direct terrestrial pathologic counterpart as the zero G environment cannot be completely replicated on Earth. Head-down tilt, bed rest studies however have been used as a terrestrial analog and produce the cephalad fluid shift. Some proposed countermeasures for SANS include vasoconstrictive thigh cuffs and lower body negative pressure. Another potential researched countermeasure is the impedance threshold device (ITD) which can reduce ICP. We review the mechanisms of the ITD and its potential use as a countermeasure for SANS.

Synergistic interplay between radiation and microgravity in spaceflight-related immunological health risks.

Spaceflight poses a myriad of environmental stressors to astronauts´ physiology including microgravity and radiation. The individual impacts of microgravity and radiation on the immune system have been extensively investigated, though a comprehensive review on their combined effects on immune system outcomes is missing. Therefore, this review aims at understanding the synergistic, additive, and antagonistic interactions between microgravity and radiation and their impact on immune function as observed during spaceflight-analog studies such as rodent hindlimb unloading and cell culture rotating wall vessel models. These mimic some, but not all, of the physiological changes observed in astronauts during spaceflight and provide valuable information that should be considered when planning future missions. We provide guidelines for the design of further spaceflight-analog studies, incorporating influential factors such as age and sex for rodent models and standardizing the longitudinal evaluation of specific immunological alterations for both rodent and cellular models of spaceflight exposure.

Optimizing healthcare in space: the role of ultrasound imaging in medical conditions.

In the context of long-distance space travel, managing medical conditions presents unique challenges due to communication delays. Consequently, onboard physicians must possess proficiency in diagnostic tools such as ultrasound, which has demonstrated its efficacy in the Space. However, there is a notable lack of comprehensive discussion regarding its effectiveness in handling medical scenarios in the Space. This bibliometric and systematic review aims to provide an updated analysis of the evidence supporting the role of ultrasound imaging in diagnosing medical conditions within microgravity environments.

Sex similarities and divergences in systemic and muscle iron metabolism adaptations to extreme physical inactivity in rats.

BACKGROUND: Previous data in humans suggest that extreme physical inactivity (EPI) affects iron metabolism differently between sexes. Our objective was to deepen the underlying mechanisms by studying rats of both sexes exposed to hindlimb unloading (HU), the reference experimental model mimicking EPI. METHODS: Eight-week-old male and female Wistar rats were assigned to control (CTL) or hindlimb unloading (HU) conditions (n = 12/group). After 7 days of HU, serum, liver, spleen, and soleus muscle were removed. Iron parameters were measured in serum samples, and ICP-MS was used to quantify iron in tissues. Iron metabolism genes and proteins were analysed by RT-qPCR and Western blot. RESULTS: Compared with control males, control females exhibited higher iron concentrations in serum (+43.3%, p < 0.001), liver (LIC; +198%, P < 0.001), spleen (SIC; +76.1%, P < 0.001), and transferrin saturation (TS) in serum (+53.3%, P < 0.001), contrasting with previous observations in humans. HU rat males, but not females, exhibited an increase of LIC (+54% P < 0.001) and SIC (+30.1%, P = 0.023), along with a rise of H-ferritin protein levels (+60.9% and +134%, respectively, in liver and spleen; P < 0.05) and a decrease of TFRC protein levels (-36%; -50%, respectively, P < 0.05). HU males also exhibited an increase of splenic HO-1 and NRF2 mRNA levels, (p < 0.001), as well as HU females (P < 0.001). Concomitantly to muscle atrophy observed in HU animals, the iron concentration increased in soleus in females (+26.7, P = 0.004) while only a trend is observed in males (+17.5%, P = 0.088). In addition, the H-ferritin and myoglobin protein levels in soleus were increased in males (+748%, P < 0.001, +22%, P = 0.011, respectively) and in females (+369%, P < 0.001, +21.9%, P = 0.007, respectively), whereas TFRC and ferroportin (FPN) protein levels were reduced in males (-68.9%, P < 0.001, -76.8%, P < 0.001, respectively) and females (-75.9%, P < 0.001, -62.9%, P < 0.001, respectively). Interestingly, in both sexes, heme exporter FLVCR1 mRNA increased in soleus, while protein levels decreased (-39.9% for males P = 0.010 and -49.1% for females P < 0.001). CONCLUSIONS: Taken together, these data support that, in rats (1) extreme physical inactivity differently impacts the distribution of iron in both sexes, (2) splenic erythrophagocytosis could play a role in this iron misdistribution. The higher iron concentrations in atrophied soleus from both sexes are associated with a decoupling between the increase in iron storage proteins (i.e., ferritin and myoglobin) and the decrease in levels of iron export proteins (i.e., FPN and FLVCR1), thus supporting an iron sequestration in skeletal muscle under extreme physical inactivity.

Injury Risk Predictions in Lunar Terrain Vehicle (LTV) Extravehicular Activities (EVAs): A Pilot Study.

Extravehicular activities will play a crucial role in lunar exploration on upcoming Artemis missions and may involve astronauts operating a lunar terrain vehicle (LTV) in a standing posture. This study assessed kinematic response and injury risks using an active muscle human body model (HBM) restrained in an upright posture on the LTV by simulating dynamic acceleration pulses related to lunar surface irregularities. Linear accelerations and rotational displacements of 5 lunar obstacles (3 craters; 2 rocks) over 5 slope inclinations were applied across 25 simulations. All body injury metrics were below NASA's injury tolerance limits, but compressive forces were highest in the lumbar (250-550N lumbar, tolerance: 5300N) and lower extremity (190-700N tibia, tolerance: 1350N) regions. There was a strong association between the magnitudes of body injury metrics and LTV resultant linear acceleration (ρ = 0.70-0.81). There was substantial upper body motion, with maximum forward excursion reaching 375 mm for the head and 260 mm for the chest. Our findings suggest driving a lunar rover in an upright posture for these scenarios is a low severity impact presenting low body injury risks. Injury metrics increased along the load path, from the lower body (highest metrics) to the upper body (lowest metrics). While upper body injury metrics were low, increased body motion could potentially pose a risk of injury from flail and occupant interaction with the surrounding vehicle, suit, and restraint hardware.

The Effects of Simulated and Real Microgravity on Vascular Smooth Muscle Cells.

As considerations are being made for the limitations and safety of long-term human spaceflight, the vasculature is important given its connection to and impact on numerous organ systems. As a major constituent of blood vessels, vascular smooth muscle cells are of interest due to their influence over vascular tone and function. Additionally, vascular smooth muscle cells are responsive to pressure and flow changes. Therefore, alterations in these parameters under conditions of microgravity can be functionally disruptive. As such, here we review and discuss the existing literature that assesses the effects of microgravity, both actual and simulated, on smooth muscle cells. This includes the various methods for achieving or simulating microgravity, the animal models or cells used, and the various durations of microgravity assessed. We also discuss the various reported findings in the field, which include changes to cell proliferation, gene expression and phenotypic shifts, and renin-angiotensin-aldosterone system (RAAS), nitric oxide synthase (NOS), and Ca2+ signaling. Additionally, we briefly summarize the literature on smooth muscle tissue engineering in microgravity as well as considerations of radiation as another key component of spaceflight to contextualize spaceflight experiments, which by their nature include radiation exposure. Finally, we provide general recommendations based on the existing literature's focus and limitations.

Influence of gut microbiome on metabolic diseases: a new perspective based on microgravity.

Purpose: Microgravity, characterized by gravity levels of 10-3-10-6g, has been found to significantly impair various physiological systems in astronauts, including cardiovascular function, bone density, and metabolism. With the recent surge in human spaceflight, understanding the impact of microgravity on biological health has become paramount. Methods: A comprehensive literature search was performed using the PubMed database to identify relevant publications pertaining to the interplay between gut microbiome, microgravity, space environment, and metabolic diseases. Results: This comprehensive review primarily focuses on the progress made in investigating the gut microbiome and its association with metabolic diseases under microgravity conditions. Microgravity induces notable alterations in the composition, diversity, and functionality of the gut microbiome. These changes hold direct implications for metabolic disorders such as cardiovascular disease (CVD), bone metabolism disorders, energy metabolism dysregulation, liver dysfunction, and complications during pregnancy. Conclusion: This novel perspective is crucial for preparing for deep space exploration and interstellar migration, where understanding the complex interplay between the gut microbiome and metabolic health becomes indispensable.