Spaceflight-induced cardiac remodeling simulated by head-down bed rest in rhesus macaques and hindlimb unloading in mice is modulated by gut microbial-derived trimethylamine N-oxide

Background: Spaceflight is physically demanding and can negatively affect astronauts’ health. It has been shown that the human gut microbiota and cardiac function are affected by spaceflight and simulated spaceflight. This study investigated the effects of the gut microbiota on simulated spaceflight-induced cardiac remodeling using 10 degrees of head-down bed rest (HDBR) in rhesus macaques and 30 degrees of hindlimb unloading (HU) in mice. Results In macaques, the gut microbiota, fecal metabolites, and cardiac remodeling were markedly affected by HDBR, and there was a correlation between cardiac remodeling and the gut microbial-derived metabolite trimethylamine N-oxide. The gut microbiota and fecal metabolites in mice were also markedly affected by HU and correlated with cardiac remodeling. Cardiac remodeling in control mice was affected by the gut microbiota of HU mice and that of HU mice was protected by the gut microbiota of control mice. Conclusion The gut microbiota, fecal metabolites, and cardiac remodeling were markedly affected by HDBR in macaques and HU in mice. These results are consistent with the known effects of spaceflight and HDBR in humans. Cardiac remodeling was affected by the gut microbiota under simulated spaceflight conditions, and the gut microbial-derived trimethylamine N-oxide was correlated with cardiac remodeling. These findings suggest that spaceflight can affect cardiac remodeling by modulating the gut microbiota and fecal metabolites.