Understanding Spaceflight-Induced Oxidative Stress and the Critical Role of Diet and Microbiome.

Spaceflight exposes astronauts to multiple environmental stressors that promote oxidative stress, including ionizing radiation, microgravity, circadian rhythm disruption, and psychological stress. These factors increase the production of reactive oxygen species (ROS) and disturb redox homeostasis, potentially affecting multiple physiological systems during long-duration missions. In addition to environmental challenges, nutritional factors may further influence oxidative balance in space. Space food systems rely on long-term storage and processing, which can lead to degradation of antioxidant nutrients and alterations in dietary composition. Furthermore, spaceflight conditions may modify eating behaviors and disrupt gut microbiome composition, both of which are closely linked to host redox regulation. This review examines current knowledge on oxidative stress during spaceflight and discusses how space food systems, dietary composition, and microbiome alterations interact with spaceflight stressors to influence redox homeostasis. Potential strategies to mitigate oxidative stress are also discussed, including preservation of antioxidant nutrients, optimization of dietary composition, reduction in pro-oxidant exposures, and microbiome-targeted approaches to support astronaut health during long-duration missions.