The impact of microgravity conditions on human gut microbiome

The human gut microbiome plays a fundamental role in maintaining overall health by regulating metabolism, immune function, and neurological processes. Disruptions to its balance can lead to various health complications. Space exploration introduces unique environmental challenges, particularly microgravity, which can significantly alter the composition and functionality of the gut microbiome, with potential consequences for astronaut health. Despite increasing interest in space microbiology, the precise effects of microgravity on intestinal physiology and microbial interactions remain largely unexplored. This PhD thesis investigates the impact of microgravity on the human gut microbiome through in vitro experiments, focusing on the intestinal epithelial barrier as a key interface between host and microbes. A central aspect of this research is the lipidomic characterization of Caco-2 cells, a widely used model of human intestinal epithelial cells, exposed to simulated microgravity conditions. Lipids play a crucial role in membrane integrity, signaling pathways, and cellular metabolism, and their alterations may reflect adaptive responses to gravitational changes. By employing advanced lipidomics and metabolomics approaches, this study identifies significant changes in lipid composition and metabolism, shedding light on the molecular mechanisms by which microgravity affects gastrointestinal function. Furthermore, the research highlights specific metabolic pathways that are most sensitive to gravitational alterations, with a particular emphasis on complex lipid classes involved in inflammation, membrane dynamics, and energy homeostasis. The findings of this thesis have important implications for space medicine, as they contribute to understanding the physiological challenges astronauts may face during long- duration missions. Additionally, they provide valuable insights into the broader role of gravity in shaping microbial ecology and host-microbe interactions. Ultimately, this research lays the groundwork for the development of targeted countermeasures to mitigate the adverse effects of microgravity on gut health, ensuring the well-being of astronauts in space and advancing knowledge in human health beyond Earth's environment.