THE INTESTINAL MICROBIOTA CONTRIBUTES TO COLONIC EPITHELIAL CHANGES IN SIMULATED MICROGRAVITY MOUSE MODEL

摘要

Exposure to microgravity leads to alterations in multiple systems. But microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. The purpose of this study was to investigate whether simulated microgravity influences the homeostasis of intestinal epithelial cells and increases the susceptibility to colon inflammation. The hindlimb unloading (HU) mouse model was used to simulate the microgravity condition. Dextran sulfate sodium (DSS) was given to mice to induce colitis. Compared to the colon epithelium of ground control mice, the HU ones revealed decreased goblet cell numbers and mucin production, reduced epithelial turnover, decreased expression of genes involved in defense and inflammatory responses. HU mice also showed alterations in fecal microbiota composition with a profile characterized by the expansion of Firmicutes and decrease of Bacteroidetes. These data indicate that simulated microgravity disrupts the homeostasis of intestinal epithelial cells which may allow large quantities of bacteria having close contact with and causing damage to the epithelial cells. As a result, increased susceptibility to DSS-induced colitis was shown in HU mice. We further showed that co-housing of control mice with HU mice resulted in HU-like epithelial changes in control mice. Transplantation of feces from control to HU mice alleviated the epithelial changes in HU mice. The results indicate that HU changes intestinal microbiota, leading to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. These animal results emphasize the necessity for evaluating the astronauts' susceptibility to inflammatory bowel diseases in distant space travels.