Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation.
Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation.
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DOI：
10.1084/jem.20112408
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发表时间：
2012-05-07
期刊：
影响因子：
--
通讯作者：
van den Brink MR
中科院分区：
文献类型：
--
作者：
Jenq RR;Ubeda C;Taur Y;Menezes CC;Khanin R;Dudakov JA;Liu C;West ML;Singer NV;Equinda MJ;Gobourne A;Lipuma L;Young LF;Smith OM;Ghosh A;Hanash AM;Goldberg JD;Aoyama K;Blazar BR;Pamer EG;van den Brink MR
在人类和小鼠模型中，GVHD 与肠道微生物群组成的显着变化有关；操纵微生物群可以改变小鼠 GVHD 的严重程度。尽管人们对肠道炎症与肠道常驻微生物之间的联系越来越了解，但在肠道炎症首次发作之前对人类菌群的纵向研究尚未见报道。在这里，我们在同种异体骨髓移植（BMT）的小鼠和人类受体中证明，移植物抗宿主病（GVHD）继发的肠道炎症与肠道微生物群组成的重大变化有关。反过来，微生物群可以调节肠道炎症的严重程度。在 GVHD 小鼠模型中，我们观察到乳杆菌目总体多样性的丧失和扩张以及梭菌目的丧失。在 BMT 之前消除小鼠菌群中的乳杆菌会加重 GVHD，而重新引入乳杆菌的主要种类则可显着预防 GVHD。然后，我们对患者在 GVHD 引起的肠道炎症发作期间的肠道菌群进行了表征，并发现了与小鼠相似的模式。我们还发现同种异体 BMT 后早期微生物混乱增加是随后 GVHD 的潜在危险因素。总之，这些数据证明了肠道炎症对菌群的调节，并表明菌群调控可以减少肠道炎症并改善同种异体 BMT 接受者的预后。
GVHD is associated with significant shifts in the composition of the intestinal microbiota in human and mouse models; manipulating the microbiota can alter the severity of GVHD in mice. Despite a growing understanding of the link between intestinal inflammation and resident gut microbes, longitudinal studies of human flora before initial onset of intestinal inflammation have not been reported. Here, we demonstrate in murine and human recipients of allogeneic bone marrow transplantation (BMT) that intestinal inflammation secondary to graft-versus-host disease (GVHD) is associated with major shifts in the composition of the intestinal microbiota. The microbiota, in turn, can modulate the severity of intestinal inflammation. In mouse models of GVHD, we observed loss of overall diversity and expansion of Lactobacillales and loss of Clostridiales. Eliminating Lactobacillales from the flora of mice before BMT aggravated GVHD, whereas reintroducing the predominant species of Lactobacillus mediated significant protection against GVHD. We then characterized gut flora of patients during onset of intestinal inflammation caused by GVHD and found patterns mirroring those in mice. We also identified increased microbial chaos early after allogeneic BMT as a potential risk factor for subsequent GVHD. Together, these data demonstrate regulation of flora by intestinal inflammation and suggest that flora manipulation may reduce intestinal inflammation and improve outcomes for allogeneic BMT recipients.
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