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Is spaceflight-induced immune dysfunction linked to systemic changes in metabolism?

ABSTRACT: The Space Shuttle Atlantis launched on its final mission (STS-135) on July 8, 2011. After just under 13 days, the shuttle landed safely at Kennedy Space Center (KSC) for the last time. Female C57BL/6J mice flew as part of the Commercial Biomedical Testing Module-3 (CBTM-3) payload. Ground controls were maintained at the KSC facility. Subsets of these mice were made available to investigators as part of NASA's Bio-specimen Sharing Program (BSP). Our group characterized cell phenotype distributions and phagocytic function in the spleen, catecholamine and corticosterone levels in the adrenal glands, and transcriptomics/metabolomics in the liver. Despite decreases in most splenic leukocyte subsets, there were increases in reactive oxygen species (ROS)-related activity. Although there were increases noted in corticosterone levels in both the adrenals and liver, there were no significant changes in catecholamine levels. Furthermore, functional analysis of gene expression and metabolomic profiles suggest that the functional changes are not due to oxidative or psychological stress. Despite changes in gene expression patterns indicative of increases in phagocytic activity (e.g. endocytosis and formation of peroxisomes), there was no corresponding increase in genes related to ROS metabolism. In contrast, there were increases in expression profiles related to fatty acid oxidation with decreases in glycolysis-related profiles. Given the clear link between immune function and metabolism in many ground-based diseases, we propose a similar link may be involved in spaceflight-induced decrements in immune and metabolic function.

SUBMITTER: Pecaut MJ

PROVIDER: S-EPMC5443495 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The International Space Station (ISS) is a uniquely enclosed environment that has been continuously occupied for the last two decades. Throughout its operation, protecting the health of the astronauts on-board has been a high priority. The human microbiome plays a significant role in maintaining human health, and disruptions in the microbiome have been linked to various diseases. To evaluate the effects of spaceflight on the human microbiome, body swabs and saliva samples were collected from four ISS astronauts on consecutive expeditions. Astronaut samples were analyzed using shotgun metagenomic sequencing and microarrays to characterize the microbial biodiversity before, during, and after the astronauts' time onboard the ISS. Samples were evaluated at an individual and population level to identify changes in microbial diversity and abundance. No significant changes in the number or relative abundance of taxa were observed between collection time points when samples from all four astronauts were analyzed together. When the astronauts' saliva samples were analyzed individually, the saliva samples of some astronauts showed significant changes in the relative abundance of taxa during and after spaceflight. The relative abundance of Prevotella in saliva samples increased during two astronauts' time onboard the ISS while the relative abundance of other commensal taxa such as Neisseria, Rothia, and Haemophilus decreased. The abundance of some antimicrobial resistance genes within the saliva samples also showed significant changes. Most notably, elfamycin resistance gene significantly increased in all four astronauts post-flight and a CfxA6 beta-lactam marker significantly increased during spaceflight but returned to normal levels post-flight. The combination of both shotgun metagenomic sequencing and microarrays showed the benefit of both technologies in monitoring microbes on board the ISS. There were some changes in each astronaut's microbiome during spaceflight, but these changes were not universal for all four astronauts. Two antimicrobial resistance gene markers did show a significant change in abundance in the saliva samples of all four astronauts across their collection times. These results provide insight for future ISS microbial monitoring studies and targets for antimicrobial resistance screenings.

Project description:BACKGROUND:Space environment imposes a range of challenges to mammalian physiology and the gut microbiota, and interactions between the two are thought to be important in mammalian health in space. While previous findings have demonstrated a change in the gut microbial community structure during spaceflight, specific environmental factors that alter the gut microbiome and the functional relevance of the microbiome changes during spaceflight remain elusive. METHODS:We profiled the microbiome using 16S rRNA gene amplicon sequencing in fecal samples collected from mice after a 37-day spaceflight onboard the International Space Station. We developed an analytical tool, named STARMAPs (Similarity Test for Accordant and Reproducible Microbiome Abundance Patterns), to compare microbiome changes reported here to other relevant datasets. We also integrated the gut microbiome data with the publically available transcriptomic data in the liver of the same animals for a systems-level analysis. RESULTS:We report an elevated microbiome alpha diversity and an altered microbial community structure that were associated with spaceflight environment. Using STARMAPs, we found the observed microbiome changes shared similarity with data reported in mice flown in a previous space shuttle mission, suggesting reproducibility of the effects of spaceflight on the gut microbiome. However, such changes were not comparable with those induced by space-type radiation in Earth-based studies. We found spaceflight led to significantly altered taxon abundance in one order, one family, five genera, and six species of microbes. This was accompanied by a change in the inferred microbial gene abundance that suggests an altered capacity in energy metabolism. Finally, we identified host genes whose expression in the liver were concordantly altered with the inferred gut microbial gene content, particularly highlighting a relationship between host genes involved in protein metabolism and microbial genes involved in putrescine degradation. CONCLUSIONS:These observations shed light on the specific environmental factors that contributed to a robust effect on the gut microbiome during spaceflight with important implications for mammalian metabolism. Our findings represent a key step toward a better understanding the role of the gut microbiome in mammalian health during spaceflight and provide a basis for future efforts to develop microbiota-based countermeasures that mitigate risks to crew health during long-term human space expeditions.

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Is spaceflight-induced immune dysfunction linked to systemic changes in metabolism?

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