Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility

The immune systems can be altered by spaceflight in many aspects, but microgravity-related mucosal immune changes and its clinical significance have not been well studied. The purpose of this study was to investigate whether simulated microgravity influences the intestinal homeostasis and increases the susceptibility to colon inflammation. The hindlimb unloading (HU) mouse model was used to simulate the microgravity condition. Three percent dextran sulfate sodium (DSS) was given to mice to induce colitis. Compared to ground control (Ctrl) mice, the HU ones revealed an impaired intestinal homeostasis and increased susceptibility to DSS-induced colitis. This includes an early-onset, 4-fold expansion of segmented filamentous bacteria (SFB), more than 2-fold decrease in regulatory T (Treg) cell numbers and IL-10 production, ∼2-fold increase in colonic IL-1β expression, 2-fold increase in circulating neutrophils, and colonic neutrophil infiltration. The application of antibiotics ameliorated the Treg and IL-10 reductions but did not significantly dampen neutrophilia and elevated expression of colonic IL-1β. These results indicate that the intestinal microflora and innate immune system both respond to simulated microgravity and together, contribute to the proinflammatory shift in the gut microenvironment. The data also emphasize the necessity for evaluating the susceptibility to inflammatory bowel diseases (IBDs) in distant space travels.