Positive mood-related gut microbiota in a long-term closed environment: a multiomics study based on the "Lunar Palace 365" experiment.

BACKGROUND: Psychological health risk is one of the most severe and complex risks in manned deep-space exploration and long-term closed environments. Recently, with the in-depth research of the microbiota-gut-brain axis, gut microbiota has been considered a new approach to maintain and improve psychological health. However, the correlation between gut microbiota and psychological changes inside long-term closed environments is still poorly understood. Herein, we used the "Lunar Palace 365" mission, a 1-year-long isolation study in the Lunar Palace 1 (a closed manned Bioregenerative Life Support System facility with excellent performance), to investigate the correlation between gut microbiota and psychological changes, in order to find some new potential psychobiotics to maintain and improve the psychological health of crew members. RESULTS: We report some altered gut microbiota that were associated with psychological changes in the long-term closed environment. Four potential psychobiotics (Bacteroides uniformis, Roseburia inulinivorans, Eubacterium rectale, and Faecalibacterium prausnitzii) were identified. On the basis of metagenomic, metaproteomic, and metabolomic analyses, the four potential psychobiotics improved mood mainly through three pathways related to nervous system functions: first, by fermenting dietary fibers, they may produce short-chain fatty acids, such as butyric and propionic acids; second, they may regulate amino acid metabolism pathways of aspartic acid, glutamic acid, tryptophan, etc. (e.g., converting glutamic acid to gamma-aminobutyric acid; converting tryptophan to serotonin, kynurenic acid, or tryptamine); and third, they may regulate other pathways, such as taurine and cortisol metabolism. Furthermore, the results of animal experiments confirmed the positive regulatory effect and mechanism of these potential psychobiotics on mood. CONCLUSIONS: These observations reveal that gut microbiota contributed to a robust effect on the maintenance and improvement of mental health in a long-term closed environment. Our findings represent a key step towards a better understanding the role of the gut microbiome in mammalian mental health during space flight and provide a basis for future efforts to develop microbiota-based countermeasures that mitigate risks to crew mental health during future long-term human space expeditions on the moon or Mars. This study also provides an essential reference for future applications of psychobiotics to neuropsychiatric treatments. Video Abstract.

Microbiome dynamics during the HI-SEAS IV mission, and implications for future crewed missions beyond Earth.

BACKGROUND: Human health is closely interconnected with its microbiome. Resilient microbiomes in, on, and around the human body will be key for safe and successful long-term space travel. However, longitudinal dynamics of microbiomes inside confined built environments are still poorly understood. Herein, we used the Hawaii Space Exploration Analog and Simulation IV (HI-SEAS IV) mission, a 1 year-long isolation study, to investigate microbial transfer between crew and habitat, in order to understand adverse developments which may occur in a future outpost on the Moon or Mars. RESULTS: Longitudinal 16S rRNA gene profiles, as well as quantitative observations, revealed significant differences in microbial diversity, abundance, and composition between samples of the built environment and its crew. The microbiome composition and diversity associated with abiotic surfaces was found to be rather stable, whereas the microbial skin profiles of individual crew members were highly dynamic, resulting in an increased microbiome diversity at the end of the isolation period. The skin microbiome dynamics were especially pronounced by a regular transfer of the indicator species Methanobrevibacter between crew members within the first 200 days. Quantitative information was used to track the propagation of antimicrobial resistance in the habitat. Together with functional and phenotypic predictions, quantitative and qualitative data supported the observation of a delayed longitudinal microbial homogenization between crew and habitat surfaces which was mainly caused by a malfunctioning sanitary facility. CONCLUSIONS: This study highlights main routes of microbial transfer, interaction of the crew, and origins of microbial dynamics in an isolated environment. We identify key targets of microbial monitoring, and emphasize the need for defined baselines of microbiome diversity and abundance on surfaces and crew skin. Targeted manipulation to counteract adverse developments of the microbiome could be a highly important strategy to ensure safety during future space endeavors. Video abstract.