Preservation of the fecal microbiome is associated withreduced severity of graft-versus-host disease.

Preservation of the fecal microbiome is associated withreduced severity of graft-versus-host disease.
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DOI：
10.1182/blood.2021015352
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发表时间：
2022-12-01
期刊：
Blood
影响因子：
20.3
通讯作者：
van den Brink, Marcel R M
van den Brink, Marcel R M
中科院分区：
医学1区
文献类型：
--
作者：
Burgos da Silva, Marina;Ponce, Doris M;van den Brink, Marcel R M

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在同种异体造血细胞移植（allo-HCT）后，胃肠道（GI）经常受到急性移植物抗宿主病（aGVHD）的影响，其病理生理学与生态失调的微生物组相关。由于微生物组成沿着胃肠道的长度变化，作者假设微生物组特征与allo-HCT后器官受累的模式相关。我们评估了266个allo-HCT受体，其中1303个粪便样本通过16 S核糖体基因测序进行分析。根据aGVHD影响的器官对患者进行分类。在发病前20天，GVHD患者有较低的丰度的类梭菌的成员，较低的计数的丁酸生产者，和较低的比例严格兼性（S/F）厌氧菌相比，移植物受者是免费的GVHD。GI GVHD患者发病前微生物多样性显著减少。与孤立性上GI aGVHD患者相比，下GI aGVHD患者的S/F厌氧菌比率较低。在发病后的20天内，仅在GVHD伴GI受累的患者中观察到微生态失调，特别是那些患有下尿路疾病的患者。重要的是，梭菌和丁酸生产菌丰度以及S/F厌氧菌比是较长总生存期的预测因子;较高的丁酸生产菌丰度和较高的S/F厌氧菌比与GVHD相关死亡风险降低相关。这些发现表明，肠道微生物组可以作为患有GVHD的allo-HCT患者结局的生物标志物。
Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, the authors hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. In the 20 days prior to disease onset, GVHD patients had lower abundances of members of the class Clostridia, lower counts of butyrate producers, and lower ratios of strict-to-facultative (S/F) anaerobic bacteria compared with allograft recipients who were free of GVHD. GI GVHD patients showed significant reduction in microbial diversity preonset. Patients with lower GI aGVHD had lower S/F anaerobe ratios compared with those with isolated upper GI aGVHD. In the 20 days after disease onset, dysbiosis was observed only in GVHD patients with GI involvement, particularly those with lower-tract disease. Importantly, Clostridial and butyrate-producer abundance as well as S/F anaerobe ratio werepredictors of longer overall survival; higher abundance of butyrate producers and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD.