Host–Microbiome Crosstalk, Health Risks and Next-Generation Mitigation Strategies

Spaceflight-associated neuro-ocular syndrome (SANS), musculoskeletal atrophy, immunological dysregulation, microgravity, cosmic radiation, confinement, and nutrient-limited diets are all consequences of human spaceflight. The gut microbiota has emerged as a critical modulator of astronaut resilience, controlling SCFA production, bile acid metabolism, vitamin biosynthesis, and immunological and neuroendocrine signaling. The reduction of taxa that produce SCFA, such as Faecalibacterium prausnitzii and Roseburia spp., the growth of opportunistic infections, the decrease in microbial diversity, and the enhanced horizontal transfer of antibiotic resistance genes are all documented in spaceflight and analog investigations. These changes are linked to cardiovascular strain, bone loss, metabolic dysregulation, electrolyte imbalance, and systemic inflammation. The ISSs extreme hygiene further reduces exposure to ambient microbes, which may weaken immune function. In this study, we investigate the effects of spaceflight on the gut microbiome and astronaut health, with a focus on microbial changes associated with immunological and metabolic abnormalities. We believe that next-generation countermeasures, prebiotics, synbiotics, postbiotics, synthetic probiotics, phage therapy, and microbiome monitoring are potential options for both space missions and terrestrial healthcare.