Viral activation and ecological restructuring characterize a microbiome axis of spaceflight-associated immune activation.

Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes, which play a role in some space-derived health disorders. However, documenting the response of microbiota to spaceflight has been difficult thus far due to mission constraints that lead to limited sampling. Here, we executed a six-month longitudinal study centered on a three-day flight to quantify the high-resolution microbiome response to spaceflight. Via paired metagenomics and metatranscriptomics alongside single immune profiling, we resolved a microbiome "architecture" of spaceflight characterized by time-dependent and taxonomically divergent microbiome alterations across 750 samples and ten body sites. We observed pan-phyletic viral activation and signs of persistent changes that, in the oral microbiome, yielded plaque-associated pathobionts with strong associations to immune cell gene expression. Further, we found enrichments of microbial genes associated with antibiotic production, toxin-antitoxin systems, and stress response enriched universally across the body sites. We also used strain-level tracking to measure the potential propagation of microbial species from the crew members to each other and the environment, identifying microbes that were prone to seed the capsule surface and move between the crew. Finally, we identified associations between microbiome and host immune cell shifts, proposing both a microbiome axis of immune changes during flight as well as the sources of some of those changes. In summary, these datasets and methods reveal connections between crew immunology, the microbiome, and their likely drivers and lay the groundwork for future microbiome studies of spaceflight.
Competing Interests: BTT is compensated for consulting with Seed Health and Enzymetrics Biosciences on microbiome study design and holds an ownership stake in the former. RD and GA are employees of Seed Health and additionally hold ownership stakes. CEM is a co-Founder of Onegevity, Twin Orbit, and Cosmica Biosciences. EEA is a consultant for Thorne HealthTech. GC has conflicts. JF and MM are employees of Tempus Labs. KB, JM, AB, JZ, BL, AA, SK, and SL are employees of Element Biosciences, which sequenced a subset of samples used in this study. Unless otherwise mentioned, none of the companies listed had a role in conceiving, executing, or funding the work described here.