Spaceflight reshapes the gut microbiome: impact of microgravity and radiation on dysbiosis-associated oncogenic pathways

Human spaceflight exposes astronauts to a unique combination of environmental stressors, which can induce significant physiological and molecular changes to several organ systems with a profound effect on physiological homeostasis. Among these systems, the gut microbiome represents a highly dynamic and environmentally sensitive ecosystem whose perturbation during space missions may have significant consequences for host health. Here, we review evidence from astronaut cohorts, as well as ground-based and in-flight animal studies, demonstrating that spaceflight conditions, with a specific emphasis on microgravity and space radiation, can drive gut dysbiosis and functional microbial shifts. These changes are associated with compromised epithelial integrity, elevation of pro-inflammatory cytokines and impairment of immune surveillance, collectively creating conditions that may favor pro-oncogenic signaling and tumorigenesis. We further examine promising microbiome-targeted countermeasures as potential strategies to preserve gut microbiome homeostasis during space missions. These findings highlight the importance of managing gut health to mitigate carcinogenic risks in astronauts, providing strategies for safer and long-duration manned space exploration.