Simulated space environmental factors of weightlessness, noise and low atmospheric pressure differentially affect the diurnal rhythm and the gut microbiome

The circadian clock extensively regulates physiology and behavior. In space, astronauts encounter many environmental factors that are dramatically different from those on Earth; however, the effects of these factors on circadian rhythms and the mechanisms remain largely unknown. The present study aimed to investigate the changes in the mouse diurnal rhythm and gut microbiome under simulated space capsule conditions, including microgravity, noise and low atmospheric pressure (LAP). Noise and LAP were loaded in the capsule while the conditions in the animal room remained constant. The mice in the capsule showed disturbed locomotor rhythms and faster adaptation to a 6-h phase advance. RNA sequencing of hypothalamus samples containing the suprachiasmatic nucleus (SCN) revealed that microgravity simulated by hind limb unloading (HU) and exposure to noise and LAP led to decreases in the quantities of differentially expressed genes (DEGs), including circadian clock genes. Changes in the rhythmicity of genes implicated in pathways of cardiovascular deconditioning and more concentrated phases were found under HU or noise and LAP. Furthermore, 16S rRNA sequencing revealed dysbiosis in the gut microbiome, and noise and LAP may repress the temporal discrepancy in the microbiome community structure induced by microgravity. Changes in diurnal oscillations were observed in a number of gut bacteria with critical physiological consequences on metabolism and immunodefense. We also found that the superimposition of noise and LAP may repress normal changes in global gene expression and adaptation in the gut microbiome. Our data demonstrate that in addition to microgravity, exposure to noise and LAP affect the robustness of circadian rhythms and the community structure of the gut microbiome, and these factors may interfere with each other in their adaptation to respective conditions. These findings are important for furthering our understanding of the alterations in circadian rhythms in the complex environment of space.