The functional fermented foods containing live microorganisms and their components are necessary for the normal functioning of the human body as normal gut microbiota needs fuel from external microbial organisms and their nanostructures — membrane vesicles (MVs), excreting outside. The сoncept that MVs may contribute to astronauts’ health probably to the same extent as their parental microbial cells do and be a temporary substitute for living microbial cells until we know more about the behavior of microbes in the space environment. The advantage of MVs is that they are not alive and cannot be changed under unfavorable conditions as microbial organisms may be. As the model, we selected MVs of a robust to environmental factors kombucha multimicrobial culture (KMC), known for its health-promoting characteristics for humans. We exposed KMC on the International Space Station in a hybrid space/Mars-like environment for an initial proof-of-concept stage. In the exposure study, KMC has survived a long-term period in harsh conditions, and the MVs generated by post-flight kombucha community members did not acquire toxicity, despite the changed membrane composition in the environment imitated conditions on the Mars surface. This observation, together with our KMC metagenomic and comparative genomic analyses of the dominant KMC bacterium Komagataeibacter oboediens, showed that the ground reference sample and spaceexposed ones were similar in topology and maintained their stability. In the next stage, we assessed the fitness, safety, and biodistribution of MVs of post-flight K. oboediens and showed that they were altered, but the modifications in membrane structure did not result in toxicity acquisition. Our proof-of-concept strategy is discussed in this review in line with the literature.