IBD-Associated Atg16L1T300A Polymorphism Regulates Commensal Microbiota of the Intestine.
IBD-Associated Atg16L1T300A Polymorphism Regulates Commensal Microbiota of the Intestine.
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IBD 相关 Atg16L1T300A 多态性调节肠道共生微生物群
DOI：
10.3389/fimmu.2021.772189
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
Liu H;Gao P;Jia B;Lu N;Zhu B;Zhang F
炎症性肠病（IBD）的发展是由宿主遗传学，微生物群和整个消化道免疫系统之间的相互作用驱动的。Atg 16 L1 T300 A多态性是一种遗传因素，可增加克罗恩病发病的风险。然而，Atg 16 L1 T300 A对肠粘膜稳态的确切贡献尚不清楚。在这里，我们表明，Atg 16 L1 T300 A多态性影响肠道细菌植物群在稳定状态下。对Atg 16 L1 T300 A/T300 A小鼠肠道细菌的分析表明，与共饲养的WT小鼠相比，它们在回肠末端和结肠中都具有改变的微生物群。有趣的是，Atg 16 L1 T300 A/T300 A小鼠体内泰泽菌属、粘菌属、鲁米诺球菌科和蓝细菌的丰度显着增加，这些细菌已知与IBD相关。此外，Akkermansia，一种粘蛋白相关的细菌，在Atg 16 L1 T300 A/T300 A小鼠中大大减少。进一步的分析表明，Atg 16 L1 T300 A/T300 A小鼠的杯状细胞由于自噬缺陷而导致粘蛋白分泌减少。最后，Atg 16 L1 T300 A/T300 A小鼠在DSS结肠炎模型中比WT小鼠发生更严重的炎症。这些结果表明，Atg 16 L1 T300 A/T300 A小鼠中改变的微生物群可能是导致Atg 16 L1 T300 A携带者患克罗恩病风险的重要因素，并支持涉及特定基因-微生物相互作用的多击疾病模型。
The development of inflammatory bowel disease (IBD) is driven by the interaction among host genetics, microbiota, and the immune system of the entire digestive tract. Atg16L1T300A polymorphism is a genetic factor that confers increased risk for the pathogenesis of Crohn’s disease. However, the exact contributions of Atg16L1T300A to intestinal mucosal homeostasis are not well understood. Here we show that Atg16L1T300A polymorphism impacts commensal bacterial flora in the intestine under a steady state. Analysis of intestinal bacteria from Atg16L1T300A/T300A mice showed that they harbored an altered microbiota in both the terminal ileum and colon compared to cohoused WT mice. Interestingly, Atg16L1T300A/T300A mice harbored a significant increase in the abundance of Tyzzerella, Mucispirillum, Ruminococcaceae, and Cyanobacteria which were known associated with IBD. Moreover, Akkermansia, a bacterium that is mucin-associated, was reduced greatly in Atg16L1T300A/T300A mice. Further analysis indicated that goblet cells of Atg16L1T300A/T300A mice had diminished mucin secretion that resulted from defective autophagy. Finally, Atg16L1T300A/T300A mice developed more severe inflammation in the DSS colitis model than in WT mice. These results indicate that the altered microbiota in Atg16L1T300A/T300A mice might be an important factor that contributed to the risk of Atg16L1T300A carriers to Crohn’s disease and supports a multi-hit disease model involving specific gene–microbe interactions.