Immune system dysregulation preceding a case of laboratory-confirmed zoster/dermatitis on board the International Space Station.

A case report detailing, for the first time, a case of laboratory-confirmed zoster in an astronaut on board the International Space Station is presented. The findings of reduced T-cell function, cytokine imbalance, and increased stress hormones which preceded the event are detailed. Relevance for deep space countermeasures is discussed.

Impact of diet on human nutrition, immune response, gut microbiome, and cognition in an isolated and confined mission environment.

Long-duration spaceflight impacts human physiology, including well documented immune system dysregulation. The space food system has the potential to serve as a countermeasure to maladaptive physiological changes during spaceflight. However, the relationship between dietary requirements, the food system, and spaceflight adaptation requires further investigation to adequately define countermeasures and prioritize resources on future spaceflight missions. We evaluated the impact of an enhanced spaceflight diet, with increased quantity and variety of fruits, vegetables, fish, and other foods rich in flavonoids and omega-3 fatty acids, compared to a standard spaceflight diet on multiple health and performance outcomes in 16 subjects over four 45-day closed chamber missions in the NASA Human Exploration Research Analog (HERA). Subjects consuming the enhanced spaceflight diet had lower cholesterol levels, lower stress (i.e. cortisol levels), better cognitive speed, accuracy, and attention, and a more stable microbiome and metatranscriptome than subjects consuming the standard diet. Although no substantial changes were observed in the immune response, there were also no immune challenges, such as illness or infection, so the full benefits of the diet may not have been apparent in these analog missions. These results indicate that a spaceflight diet rich in fruits, vegetables, and omega-3 fatty acids produces significant health and performance benefits even over short durations. Further investigation is required to fully develop dietary countermeasures to physiological decrements observed during spaceflight. These results will have implications for food resource prioritization on spaceflight missions.

Response of Arabidopsis thaliana and Mizuna Mustard Seeds to Simulated Space Radiation Exposures.

One of the major concerns for long-term exploration missions beyond the Earth's magnetosphere is consequences from exposures to solar particle event (SPE) protons and galactic cosmic rays (GCR). For long-term crewed Lunar and Mars explorations, the production of fresh food in space will provide both nutritional supplements and psychological benefits to the astronauts. However, the effects of space radiation on plants and plant propagules have not been sufficiently investigated and characterized. In this study, we evaluated the effect of two different compositions of charged particles-simulated GCR, and simulated SPE protons on dry and hydrated seeds of the model plant Arabidopsis thaliana and the crop plant Mizuna mustard [Brassica rapa var. japonica]. Exposures to charged particles, simulated GCRs (up to 80 cGy) or SPEs (up to 200 cGy), were performed either acutely or at a low dose rate using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Lab (BNL). Control and irradiated seeds were planted in a solid phytogel and grown in a controlled environment. Five to seven days after planting, morphological parameters were measured to evaluate radiation-induced damage in the seedlings. After exposure to single types of charged particles, as well as to simulated GCR, the hydrated Arabidopsis seeds showed dose- and quality-dependent responses, with heavier ions causing more severe defects. Seeds exposed to simulated GCR (dry seeds) and SPE (hydrated seeds) had significant, although much less damage than seeds exposed to heavier and higher linear energy transfer (LET) particles. In general, the extent of damage depends on the seed type.

Bellagio II Report: Terrestrial Applications of Space Medicine Research.

AbstractINTRODUCTION: For over 50 yr, investigators have studied the physiological adaptations of the human system during short- and long-duration spaceflight exposures. Much of the knowledge gained in developing health countermeasures for astronauts onboard the International Space Station demonstrate terrestrial applications. To date, a systematic process for translating these space applications to terrestrial human health has yet to be defined.METHODS: In the summer of 2017, a team of 38 international scientists launched the Bellagio ll Summit Initiative. The goals of the Summit were: 1) To identify space medicine findings and countermeasures with highest probability for future terrestrial applications; and 2) To develop a roadmap for translation of these countermeasures to future terrestrial application. The team reviewed public domain literature, NASA databases, and evidence books within the framework of the five-stage National Institutes of Health (NIH) translation science model, and the NASA two-stage translation model. Teams then analyzed and discussed interdisciplinary findings to determine the most significant evidence-based countermeasures sufficiently developed for terrestrial application.RESULTS: Teams identified published human spaceflight research and applied translational science models to define mature products for terrestrial clinical practice.CONCLUSIONS: The Bellagio ll Summit identified a snapshot of space medicine research and mature science with the highest probability of translation and developed a Roadmap of terrestrial application from space medicine-derived countermeasures. These evidence-based findings can provide guidance regarding the terrestrial applications of best practices, countermeasures, and clinical protocols currently used in spaceflight.Sides MB, Johnston SL III, Sirek A, Lee PH, Blue RS, Antonsen EL, Basner M, Douglas GL, Epstein A, Flynn-Evans EE, Gallagher MB, Hayes J, Lee SMC, Lockley SW, Monseur B, Nelson NG, Sargsyan A, Smith SM, Stenger MB, Stepanek J, Zwart SR; Bellagio II Team. Bellagio II report: terrestrial applications of space medicine research. Aerosp Med Hum Perform. 2021; 92(8):650669.

Impact of galactic cosmic ray simulation on nutritional content of foods.

Foods packaged for future deep-space exploration missions may be prepositioned ahead of astronaut arrival and will be exposed to galactic cosmic rays (GCRs) and solar radiation in deep space at higher levels and different spectrums than those found in low-Earth orbit (LEO). In this study, we have evaluated the impact of a GCR simulation (approximately 0.5 and 5 Gy doses) at the NASA Space Radiation Laboratory (NSRL) on two retort thermostabilized food products that are good sources of radiation labile nutrients (thiamin, vitamin E, or unsaturated fats). No trends or nutritional differences were found between the radiation-treated samples and the control immediately after treatment or one-year after treatment. Small changes in a few nutrients were measured following one-year of storage. Further studies may be needed to confirm these results, as the foods in this study were heterogeneous, and this may have masked meaningful changes due to pouch-to-pouch variations.

Countermeasures-based Improvements in Stress, Immune System Dysregulation and Latent Herpesvirus Reactivation onboard the International Space Station - Relevance for Deep Space Missions and Terrestrial Medicine.

The International Space Station (ISS) has continued to evolve from an operational perspective and multiple studies have monitored both stress and the immune system of ISS astronauts. Alterations were ascribed to a potentially synergistic array of factors, including microgravity, radiation, psychological stress, and circadian misalignment. Comparing similar data across 12 years of ISS construction and operations, we report that immunity, stress, and the reactivation of latent herpesviruses have all improved in ISS astronauts. Major physiological improvements seem to have initiated approximately 2012, a period coinciding with improvements onboard ISS including cargo delivery and resupply frequency, personal communication, exercise equipment and protocols, food quality and variety, nutritional supplementation, and schedule management. We conclude that spaceflight associated immune dysregulation has been positively influenced by operational improvements and biomedical countermeasures onboard ISS. Although an operational challenge, agencies should therefore incorporate, within vehicle design limitations, these dietary, operational, and stress-relieving countermeasures into deep space mission planning. Specific countermeasures that have benefited astronauts could serve as a therapy augment for terrestrial acquired immunodeficiency patients.

Meal replacement in isolated and confined mission environments: Consumption, acceptability, and implications for physical and behavioral health.

Strategies that reduce food system mass without negatively impacting food intake, acceptability, and resulting astronaut health and performance are essential for mission success in extreme operational environments such as space exploration. Here, we report the impact of substituting the spaceflight standard breakfast with energy equivalent, calorically-dense meal replacement bars (MRBs) on consumption, acceptability, and satiety and on associations with physical and behavioral health outcomes in high-performing subjects completing 30-day missions in the isolated and confined operational environment of NASA's Human Exploration Research Analog (HERA) habitat. MRB implementation was associated with reduced daily caloric intake, weight loss, and decrements in mood and neurobehavioral functioning, with no significant impacts on somatic symptoms and physical functioning. Food acceptability ratings suggest that flavor, texture, and menu fatigue attributed to limited variety are contributing factors, which are exacerbated by a daily implementation schedule. Meal replacement strategies for short-duration missions are operationally feasible, moderately acceptable, and can contribute to the practical goal of mass reduction, but more work is needed to define and optimize flavors, variety, and implementation schedules that sustain adequate nutrition, physical and behavioral health, and operational performance over time in isolated, confined, and extreme mission environments.

The Behavioral Biology of Teams: Multidisciplinary Contributions to Social Dynamics in Isolated, Confined, and Extreme Environments.

Teams in isolated, confined, and extreme (ICE) environments face many risks to behavioral health, social dynamics, and team performance. Complex long-duration ICE operational settings such as spaceflight and military deployments are largely closed systems with tightly coupled components, often operating as autonomous microsocieties within isolated ecosystems. As such, all components of the system are presumed to interact and can positively or negatively influence team dynamics through direct or indirect pathways. However, modern team science frameworks rarely consider inputs to the team system from outside the social and behavioral sciences and rarely incorporate biological factors despite the brain and associated neurobiological systems as the nexus of input from the environment and necessary substrate for emergent team dynamics and performance. Here, we provide a high-level overview of several key neurobiological systems relevant to social dynamics. We then describe several key components of ICE systems that can interact with and on neurobiological systems as individual-level inputs influencing social dynamics over the team life cycle-specifically food and nutrition, exercise and physical activity, sleep/wake/work rhythms, and habitat design and layout. Finally, we identify opportunities and strategic considerations for multidisciplinary research and development. Our overarching goal is to encourage multidisciplinary expansion of team science through (1) prospective horizontal integration of variables outside the current bounds of team science as significant inputs to closed ICE team systems and (2) bidirectional vertical integration of biology as the necessary inputs and mediators of individual and team behavioral health and performance. Prospective efforts to account for the behavioral biology of teams in ICE settings through an integrated organizational neuroscience approach will enable the field of team science to better understand and support teams who work, live, serve, and explore in extreme environments.

Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions.

Recent studies have established that dysregulation of the human immune system and the reactivation of latent herpesviruses persists for the duration of a 6-month orbital spaceflight. It appears certain aspects of adaptive immunity are dysregulated during flight, yet some aspects of innate immunity are heightened. Interaction between adaptive and innate immunity also seems to be altered. Some crews experience persistent hypersensitivity reactions during flight. This phenomenon may, in synergy with extended duration and galactic radiation exposure, increase specific crew clinical risks during deep space exploration missions. The clinical challenge is based upon both the frequency of these phenomena in multiple crewmembers during low earth orbit missions and the inability to predict which specific individual crewmembers will experience these changes. Thus, a general countermeasure approach that offers the broadest possible coverage is needed. The vehicles, architecture, and mission profiles to enable such voyages are now under development. These include deployment and use of a cis-Lunar station (mid 2020s) with possible Moon surface operations, to be followed by multiple Mars flyby missions, and eventual human Mars surface exploration. Current ISS studies will continue to characterize physiological dysregulation associated with prolonged orbital spaceflight. However, sufficient information exists to begin consideration of both the need for, and nature of, specific immune countermeasures to ensure astronaut health. This article will review relevant in-place operational countermeasures onboard ISS and discuss a myriad of potential immune countermeasures for exploration missions. Discussion points include nutritional supplementation and functional foods, exercise and immunity, pharmacological options, the relationship between bone and immune countermeasures, and vaccination to mitigate herpes (and possibly other) virus risks. As the immune system has sentinel connectivity within every other physiological system, translational effects must be considered for all potential immune countermeasures. Finally, we shall discuss immune countermeasures in the context of their individualized implementation or precision medicine, based on crewmember specific immunological biases.

Initial assessment of the nutritional quality of the space food system over three years of ambient storage.

Processed and prepackaged space food is the main source of nutrition for crew aboard the International Space Station, and likely will continue to be the main source of nutrition for future exploration missions. However, very little information is available on the nutritional stability of space foods. To better understand their nutritional stability, 24 micronutrients were measured in 109 space foods stored over 3 years at room temperature. Our analysis indicated that potassium, calcium, vitamin D, and vitamin K concentrations in the food may not be adequate to meet the recommended daily intake requirements even before storage. Decreases in vitamins A, C, B1, and B6 were observed during storage. Notably, vitamins B1 and C may degrade to inadequate levels after 1 year and 3 years, respectively. This assessment suggests that different technological approaches will be required to stabilize processed foods to enable spaceflight missions over 1 year.

Directed chromosomal integration and expression of the reporter gene gusA3 in Lactobacillus acidophilus NCFM.

Lactobacillus acidophilus NCFM is a probiotic microbe that survives passage through the human gastrointestinal tract and interacts with the host epithelium and mucosal immune cells. The potential for L. acidophilus to express antigens at mucosal surfaces has been investigated with various antigens and plasmid expression vectors. Plasmid instability and antibiotic selection complicate the possibility of testing these constructs in human clinical trials. Integrating antigen encoding genes into the chromosome for expression is expected to eliminate selection requirements and provide genetic stability. In this work, a reporter gene encoding a ß-glucuronidase (GusA3) was integrated into four intergenic chromosomal locations. The integrants were tested for genetic stability and GusA3 activity. Two locations were selected for insertion downstream of constitutively highly expressed genes, one downstream of slpA (LBA0169), encoding a highly expressed surface-layer protein, and one downstream of phosphopyruvate hydratase (LBA0889), a highly expressed gene with homologs in other lactic acid bacteria. An inducible location was selected downstream of lacZ (LBA1462), encoding a ß-galactosidase. A fourth location was selected in a low-expression region. The expression of gusA3 was evaluated from each location by measuring GusA3 activity on 4-methyl-umbelliferyl-ß-d-glucuronide (MUG). GusA3 activity from both highly expressed loci was more than three logs higher than the gusA3-negative parent, L. acidophilus NCK1909. GusA3 activity from the lacZ locus was one log higher in cells grown in lactose than in glucose. The differences in expression levels between integration locations highlights the importance of rational targeting with gene cassettes intended for chromosomal expression.

Integrative food grade expression system for lactic acid bacteria.

Lactobacillus acidophilus NCFM is a probiotic microbe with the ability to survive passage to the -gastrointestinal tract, interact intimately with the host and induce immune responses. The genome of NCFM has been determined and the bacterium is genetically accessible. Therefore, L. acidophilus has excellent potential for use as a vaccine delivery vehicle to express antigens at mucosal surfaces. Plasmids, commonly used to carry antigen encoding genes, are inherently unstable and require constant selection by antibiotics, which can be problematic for in vivo studies and clinical trials. Chromosomal expression of gene cassettes encoding antigens offers enhanced genetic stability by eliminating requirements for marker selection. This work illustrates the integration and inducible expression of the reporter gene gusA3, -encoding a ß-glucuronidase (GusA3), in the L. acidophilus chromosome. A previously described upp-counterselectable gene replacement system was used to direct insertion of the gusA3 gene into an intergenic chromosomal location downstream of lacZ (LBA1462), encoding a ß-galactosidase. The transcriptional activity of integrated gusA3 was evaluated by GUS activity assays using 4-methyl-umbelliferyl-ß-D: -glucuronide (MUG) and was determined to be one to two orders of magnitude higher than the GusA3-negative parent, NCK1909. The successful chromosomal integration and expression of GusA3 demonstrate the potential of this method for higher levels of inducible gene expression in L. acidophilus.

Developing the NASA food system for long-duration missions.

Even though significant development has transformed the space food system over the last 5 decades to attain more appealing dietary fare for low-orbit space crews, the advances do not meet the need for crews that might travel to Mars and beyond. It is estimated that a food system for a long-duration mission must maintain organoleptic acceptability, nutritional efficacy, and safety for a 3- to 5-y period to be viable. In addition, the current mass and subsequent waste of the food system must decrease significantly to accord with the allowable volume and payload limits of the proposed future space vehicles. Failure to provide the appropriate food or to optimize resource utilization introduces the risk that an inadequate food system will hamper mission success and/or threaten crew performance. Investigators for the National Aeronautics and Space Administration (NASA) Advanced Food Technology (AFT) consider identified concerns and work to mitigate the risks to ensure that any new food system is adequate for the mission. Yet, even with carefully planned research, some technological gaps remain. NASA needs research advances to develop food that is nutrient-dense and long-lasting at ambient conditions, partial gravity cooking processes, methods to deliver prescribed nutrients over time, and food packaging that meets the mass, barrier, and processing requirements of NASA. This article provides a brief review of research in each area, details the past AFT research efforts, and describes the remaining gaps that present barriers to achieving a food system for long exploration missions.

Genomic evolution of domesticated microorganisms.

Strains of lactic acid bacteria, yeasts, and molds have been selected over thousands of years based on the unique sensory attributes they provide to food fermentations. Over the centuries they have evolved to their domesticated roles, leading to genome decay, loss of pathways, acquisition of genomic elements, and beneficial mutations that provide an advantage in their nutrient-rich food environments. This review highlights the evolutionary traits influenced by the domestication process as these microbes adapted to nutrient-rich foods developed by humans.