Metabolomic and Lipidomic Signatures of Spaceflight and Space-Analog Conditions

Introduction: Spaceflight and space-analog environments expose biological systems to microgravity, radiation, isolation, confinement, and circadian disruption, leading to systemic physiological adaptations that may be captured by metabolomics and lipidomics. However, available evidence remains fragmented across biological models, matrices, analytical platforms, and mission-related stressors. This systematic review aimed to synthesize metabolomic and lipidomic alterations reported under spaceflight, microgravity, and space-analog conditions.

Methods: A PubMed-based systematic review was conducted following PRISMA 2020 principles. Searches combined terms related to metabolomics, lipidomics, spaceflight, microgravity, simulated microgravity, bed rest, hindlimb unloading, astronauts, and space analogs. Original studies were eligible if they reported metabolomic, lipidomic, sphingolipidomic, or multi-omic data including metabolite-level outcomes in humans, mammalian models, or mammalian cells exposed to space-relevant conditions. Reviews, editorials, plant-only studies, microbial-only studies, and studies without metabolomics/lipidomics were excluded.

Results: Twenty-two original studies were included in the qualitative synthesis. Evidence consistently indicated alterations in mitochondrial and energy metabolism, amino acid turnover, lipid remodeling, sphingolipid metabolism, sulfur metabolism, oxidative stress, gut microbiome–metabolome interactions, musculoskeletal adaptation, renal dysfunction, and immune-cell metabolic reprogramming. Human astronaut studies suggested mission-related and sex-specific metabolic adjustments, while animal, bed-rest, hindlimb unloading, and cellular models provided mechanistic insights into tissue-specific responses to microgravity and associated stressors.

Conclusions: Spaceflight and space-analog conditions are associated with convergent metabolomic and lipidomic signatures reflecting multisystem adaptation. These findings support metabolomics as a promising tool for astronaut health monitoring, biomarker discovery, and development of countermeasures for long-duration space missions.