Dynamics of the Stool Virome in Very Early-Onset Inflammatory Bowel Disease
Dynamics of the Stool Virome in Very Early-Onset Inflammatory Bowel Disease
复制标题
DOI：
10.1093/ecco-jcc/jjaa094
复制
发表时间：
2020-11-01
影响因子：
8
通讯作者：
Bushman, Frederic D.
中科院分区：
文献类型：
--
作者：
Liang, Guanxiang;Conrad, Maire A.;Bushman, Frederic D.
背景和目的：肠道菌群失调是炎症性肠病[IBD]发病机制的一个众所周知的相关因素。然而，很少有研究检查了极早发型[VEO] IBD的微生物组，其定义为6岁之前IBD的发作。在这里，我们专注于微生物组的病毒部分-病毒组-以评估病毒与疾病过程的可能关联，推理任何可能与IBD相关的病毒可能在年轻受试者中生长更稳健，因此更容易检测到。从收集自VEO-IBD患者[n= 54]和健康对照[n = 23]的粪便样品中纯化病毒样颗粒[VLP]，结果：VEO-IBD患者VLP总数与健康对照组相比无显著性差异。对于细菌病毒，发现VEO-IBD受试者与健康对照相比具有更高的尾病毒目与微病毒科的比率。尾状病毒目的增加也与免疫抑制治疗有关。对于感染人类细胞的病毒，与健康对照相比，在VEO-IBD中显示出更高的流行率。在VEO-IBD组中，较高水平的指环病毒DNA也与免疫抑制治疗呈正相关。为了寻找新的病毒，短序列丰富的VEO-IBD样品进行了鉴定，有些可以在一个独立的队列中进行验证，虽然没有明确的病毒，这提供了序列标签，以询问在未来的study.Conclusions：这些数据因此文件扰动与VEO-IBD相关的正常病毒种群，并提供了一个生物标记-Anelloviridae DNA水平，可能有用的免疫抑制的有效性报告。
Background and Aims: Dysbiosis of the gut microbiota is a well-known correlate of the pathogenesis of inflammatory bowel disease [IBD]. However, few studies have examined the microbiome in very early-onset [VEO] IBD, which is defined as onset of IBD before 6 years of age. Here we focus on the viral portion of the microbiome-the virome-to assess possible viral associations with disease processes, reasoning that any viruses potentially associated with IBD might grow more robustly in younger subjects, and so be more detectable.Methods: Virus-like particles [VLPs] were purified from stool samples collected from patients with VEO-IBD [n= 54] and healthy controls [n = 23], and characterized by DNA and RNA sequencing and VLP particle counts.Results: The total number of VLPs was not significantly different between VEO-IBD and healthy controls. For bacterial viruses, theVEO-IBD subjects were found to have a higher ratio of Caudovirales vs to Microviridae compared to healthy controls. An increase in Caudovirales was also associated with immunosuppressive therapy. For viruses infecting human cells, Anelloviridae showed higher prevalence in VEO-IBD compared to healthy controls. Within the VEO-IBD group, higher levels of Anelloviridae DNA were also positively associated with immunosuppressive treatment. To search for new viruses, short sequences enriched in VEO-IBD samples were identified, and some could be validated in an independent cohort, although none was clearly viral; this provides sequence tags to interrogate in future studies.Conclusions: These data thus document perturbations to normal viral populations associated with VEO-IBD, and provide a biomarker-Anelloviridae DNA levels-potentially useful for reporting the effectiveness of immunosuppression.