Exposure to space environment induces alterations in glucose and lipid metabolism that contribute to muscular atrophy, bone loss, and cardiovascular disorders. Intestinal microbiota is also changed, but its impact on spaceflight‐related metabolic disorder is not clear. We investigated the relationship between glucose metabolic changes and gut dysbiosis in a hind limb‐unloading (HU) mouse model, a well‐accepted ground‐based spaceflight analog. Impaired body weight gain, glucose intolerance, and peripheral insulin resistance were found in 2–4‐wk HU mice. Reduced abundance of gut Bifidobacterium spp. and Akkermansia muciniphila was observed within 3 d of HU. The ground‐based control (Ctrl) mice that were cohoused with HU mice showed similar patterns of dysbiosis and metabolic changes. Compared with the Ctrls, higher levels of plasma LPS‐binding protein and altered transcription of Tnfa and glucose metabolism‐related genes in the liver were observed in HU mice. The supplementation of Bifidobacterium spp. suppressed endotoxemia and liver inflammation and improved glucose tolerance in HU mice. The results indicate a close relationship between dysbiosis and altered glucose metabolism in the HU model and also emphasize the importance of evaluating intestinal microbiota in astronauts and its effect on glucose metabolism.—Wang, Y., Zhao, W., Shi, J., Wang, J., Hao, J., Pang, X., Huang, X., Chen, X., Li, Y., Jin, R., Ge, Q. Intestinal microbiota contributes to altered glucose metabolism in simulated microgravity mouse model. FASEB J. 33, 10140–10151 (2019). http://www.fasebj.org

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.

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. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium-induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HUlike epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts' intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model. FASEB J. 31, 3695-3709 (2017 Exposure to microgravity leads to alterations, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and immune dysfunction, in multiple systems (1). Limited reports also suggest that spaceflight and microgravity affect the integrity of intestinal epithelium. For instance, reduced length of villi and depth of crypts was found in rats that were flown on 12-d Cosmos 2044 and Foton M3 missions (2, 3), and decreased mucin production of intestinal epithelial cells was shown in rats that were flown on the 19.5-d Cosmos 605 mission (4). Colonic TGF-b expression was altered in mice aboard the 13-d STS-135 or 91-d International Space Station missions (5, 6). Using a well-accepted, ground-based spaceflight analog, the hindlimb unloading (HU) mouse model (7) found that simulated microgravity resulted in a transient increase in intestinal permeability, which is characterized by the elevation of circulating LPS and the activation of the innate immune system. The clinical significance and mechanism of these epithelial changes are not clear; however, Chopra et al. (8) reported that HU mice that were infected with Salmonella enterica serovar typhimurium had a 100-fold decrease in LD 50 compared with normal-gravity control (Ctrl) mice. This indicates that microgravity-induced intestinal epithelial changes may exacerbate bacte...

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Toona sinensis Roem, also known as Chinese Toona, belonging to the family Meliaceae, is widely distributed in North China and Southeast China, especially in Gansu, Hebei and Shandong Provinces. It is a rapidly growing, perennial deciduous tree vegetable and its fresh, young leaves and shoots are edible and nutritious. More importantly, almost all parts of T. sinensis including seeds, bark, root bark, petioles and leaves have medicinal effects to human health 1-3. Its leaves has been used for the treatments of enteritis, dysentery, carbuncles, boils, dermatitis, scabies, tinea blanca, heliosis and for the health improvement as a traditional Chinese medicine 4. The bark is used as an astringent and as a depurative substance, the powdered root is used as a corrective and the fruits are used as an astringent and for the treatment of eye infection 5. As far as our literature survey could ascertain, the antimicrobial activity of essential oil has not been published previously, although there are some reports on the essential oil composition isolated from this species 6,7. Therefore, we focused our study on the chemical composition and antimicrobial properties of the essential oil of the leaves of T. sinensis from China. EXPERIMENTAL The leaves of T. sinensis Roem were collected during germination stage in May 2011 from Qingyang in Gansu province, China.