Intestinal Microbiota Can Predict Acute Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation
Intestinal Microbiota Can Predict Acute Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation
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肠道微生物群可以预测异基因造血干细胞移植后的急性移植物抗宿主病
DOI：
10.1016/j.bbmt.2019.07.006
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发表时间：
2019-10-01
影响因子：
4.3
通讯作者：
Liu, Qifa
中科院分区：
文献类型：
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作者：
Han, Lijie;Zhang, Haiyan;Liu, Qifa
肠道微生物组在急性移植物抗宿主病（aGVHD）的发展中起重要作用。然而，肠道微生物群是否可以预测aGVHD的发展很少报道。在这里，我们对141例异基因造血干细胞移植后的微生物群进行了前瞻性研究。我们发现aGVHD组在第0天和第15 +/- 1天的微生物群多样性低于非aGVHD组（分别为P = 0.018和0.009）。多样性与预处理强度（P = 0.017，第0天; P = 0.045，第15天）和β-内酰胺类抗生素给药（P = 0.004，第15天）呈负相关。强化预处理和β-内酰胺类抗生素与第15天较低的调节性T（Treg）/辅助性T细胞17（Th 17）比率相关（分别为P = 0.030和0.047）。在第15天，与标准组相比，强化预处理组的炎症因子（肿瘤坏死因子α、白细胞介素[IL]-6、IL-17 A、IL-1 β和脂多糖）水平更高（P <0.05）。累积肠道微生物群（AIM）评分定义为移植后第15天4种细菌（毛螺菌科、消化链球菌科、丹毒丝菌科和肠杆菌科）的微生物群多样性和梯度。AIM评分与aGVHD分级呈正相关（r = 0.481，P <0.001），AIM评分可预测aGVHD的发展（II-IV级aGVHD：曲线下面积[AUC]，0.75，P <0.001; III-IV级aGVHD：AUC，0.84，P <0.001）。这些发现表明肠道微生物群和条件化可能通过炎症因子和Treg/Th 17平衡诱导aGVHD。中性粒细胞植入时肠道菌群的构成可以预测aGVHD的发展。(C)2019年美国移植和细胞治疗学会。爱思唯尔公司出版
The intestinal microbiome plays an important role in the development of acute graft-versus-host disease (aGVHD). However, whether intestinal microbiota can predict the development of aGVHD has been reported only rarely. Here we conducted a prospective study of microbiota in 141 patients after allogeneic hematopoietic stem cell transplantation. We found lower microbiota diversity in the aGVHD group compared with the non-aGVHD group at day 0 and day 15 +/- 1 (P = .018 and .009, respectively). Diversity was negatively associated with conditioning intensity (P = .017, day 0; P = .045, day 15) and beta-lactam antibiotic administration (P = .004, day 15). Intensified conditioning and beta-lactam antibiotics were associated with a lower regulatory T (Treg)/T helper 17 (Th17) cell ratio at day 15 (P = .030 and .047, respectively). At day 15, the levels of the inflammatory factors (tumor necrosis factor a, interleukin [IL]-6, IL-17A, IL-1 beta, and lipopolysaccharide) were higher in the intensified conditioning group compared with the standard group (P < .05). The accumulated intestinal microbiota (AIM) score was defined as microbiota diversity and gradient of the 4 bacterials (Lachnospiraceae, Peptostreptococcaceae, Erysipelotrichaceae, and Enterobacteriaceae) at day 15 post-transplantation. The AIM score was positively correlated with aGVHD grade (r = .481, P < .001), and the AIM score could be predictive of the development of aGVHD (grade II-IV aGVHD: area under the curve [AUC], .75, P < .001; grade III-IV aGVHD: AUC, .84, P < .001). These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment may predict the development of aGVHD. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.