Much attention has been focused on the role of the bacterial microbiome in human health, but the virome is understudied. Although previously investigated in individuals with inflammatory bowel diseases or solid-organ transplants, virome dynamics in allogeneic hematopoietic stem cell transplantation (HSCT) and enteric graft-versus-host disease (GVHD) remain unexplored. Here we characterize the longitudinal gut virome in 44 recipients of HSCT using metagenomics. A viral 'bloom' was identified, and significant increases were demonstrated in the overall proportion of vertebrate viral sequences following transplantation (P = 0.02). Increases in both the rates of detection (P < 0.0001) and number of sequences (P = 0.047) of persistent DNA viruses (anelloviruses, herpesviruses, papillomaviruses and polyomaviruses) over time were observed in individuals with enteric GVHD relative to those without, a finding accompanied by a reduced phage richness (P = 0.01). Picobirnaviruses were detected in 18 individuals (40.9%), more frequently before or within a week after transplant than at later time points (P = 0.008). In a time-dependent Cox proportional-hazards model, picobirnaviruses were predictive of the occurrence of severe enteric GVHD (hazard ratio, 2.66; 95% confidence interval (CI) = 1.46-4.86; P = 0.001), and correlated with higher fecal levels of two GVHD severity markers, calprotectin and α1-antitrypsin. These results reveal a progressive expansion of vertebrate viral infections over time following HSCT, and they suggest an unexpected association of picobirnaviruses with early post-transplant GVHD.

中文翻译：

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造血干细胞移植中的真核肠道病毒：肠移植物抗宿主病的新线索。

人们已经将许多注意力集中在细菌微生物组在人类健康中的作用上，但是对病毒的研究却不足。尽管以前曾在患有炎症性肠病或实体器官移植的患者中进行过调查，但在同种异体造血干细胞移植（HSCT）和肠移植物抗宿主病（GVHD）中的病毒动力学仍未得到研究。在这里，我们使用宏基因组学对44位HSCT接受者的纵向肠道病毒进行了表征。鉴定出病毒“花”，移植后脊椎动物病毒序列的总体比例显着增加（P = 0.02）。持久性DNA病毒（无城ello病毒，疱疹病毒，相对于没有肠道GVHD的个体，随着时间的推移观察到了肠道GVHD个体的乳头瘤病毒和多瘤病毒（P = 0.01）。在移植前或移植后一周内，在18个个体中检出了小核糖核酸病毒（占40.9％），而在以后的时间点则更显着（P = 0.008）。在具有时间依赖性的Cox比例风险模型中，小核糖核酸病毒可预测严重肠GVHD的发生（风险比2.66； 95％置信区间（CI）= 1.46-4.86; P = 0.001），并与粪便水平升高相关两种GVHD严重性指标，钙卫蛋白和α1-抗胰蛋白酶。这些结果表明，HSCT后，随着时间的推移，脊椎动物病毒感染会逐渐扩大，并且它们表明小核糖核酸病毒与移植后早期的GVHD发生了意外的关联。