Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility
Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility
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模拟微重力会破坏肠道稳态并增加结肠炎的易感性。
DOI：
10.1096/fj.15-271700
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发表时间：
2015-08-01
期刊：
影响因子：
4.8
通讯作者：
Ge, Qing
中科院分区：
文献类型：
--
作者：
Li, Pingping;Shi, Junxiu;Ge, Qing
航天飞行对机体免疫系统的影响是多方面的，但与微重力相关的黏膜免疫改变及其临床意义尚未得到充分研究。本研究的目的是探讨模拟微重力是否会影响肠道内稳态，增加结肠炎症的易感性。采用后肢去负荷（HU）小鼠模型模拟微重力条件。给小鼠注射3%葡聚糖硫酸钠（DSS）诱导结肠炎。与地面对照（Ctrl）小鼠相比，HU小鼠显示肠道稳态受损，对DSS诱导的结肠炎的易感性增加。这包括分节丝状细菌（SFB）的早发性4倍扩增，调节性T（T-reg）细胞数量和IL-10产生减少2倍以上，类似于结肠IL-1 β表达增加2倍，循环中性粒细胞增加2倍，以及结肠中性粒细胞浸润。抗生素的应用改善了T-reg和IL-10的降低，但没有显著抑制嗜中性粒细胞和结肠IL-1 β的表达升高。这些结果表明，肠道微生物菌群和先天免疫系统都对模拟微重力作出反应，并共同促进肠道微环境中的促炎性转变。这些数据还强调了在遥远的太空旅行中评估炎症性肠病（IBD）易感性的必要性。
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 (T-reg) cell numbers and IL-10 production, similar to 2-fold increase in colonic IL-1 beta expression, 2-fold increase in circulating neutrophils, and colonic neutrophil infiltration. The application of antibiotics ameliorated the T-reg and IL-10 reductions but did not significantly dampen neutrophilia and elevated expression of colonic IL-1 beta. 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.