KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Viral Metagenomics, Leuven, Belgium.
KU Leuven, Department of Microbiology Immunology and Transplantation, Rega Institute, Laboratory of Molecular Bacteriology, Leuven, Belgium.
J Crohns Colitis. 2023 Oct 20;17(9):1504-1513. doi: 10.1093/ecco-jcc/jjad061.
Inflammatory bowel disease [IBD] is a major debilitating disease. Recently, the gut microbiota has gained attention as an important factor involved in the pathophysiology of IBD. As a complement to the established bacterial 'enterotypes' associated with IBD, we focused here on viruses. We investigated the intestinal virome of IBD patients undergoing biological therapy for the presence of virome configurations associated with IBD, and to uncover how those configurations are associated with therapeutic success.
Viral-like particle enrichment followed by deep sequencing was performed on 432 faecal samples from 181 IBD patients starting biological therapy. Redundancy analysis and Dirichlet Multinomial Mixtures were applied to determine covariates of the virome composition and to condense the gut virota into 'viral community types', respectively.
Patients were stratified based on unsupervised clustering into two viral community types. Community type CA showed a low α-diversity and a high relative abundance of Caudoviricetes [non-CrAss] phages and was associated with the dysbiotic Bact2-enterotype. Community type CrM showed a high α-diversity and a high relative abundance of Crassvirales and Malgrandaviricetes phages. During post-interventional analysis, endoscopic outcome was associated with gut virome composition. Remitting UC patients had a high percentage of community type CrM, a high Shannon diversity and a low lysogenic potential. Pre-interventional analyses also identified five novel phages associated with treatment success.
This study proposed two gut virome configurations that may be involved in the pathophysiology of IBD. Interestingly, those viral configurations are further associated with therapeutic success, suggesting a potential clinical relevance.
炎症性肠病（IBD）是一种严重的致残性疾病。最近，肠道微生物群作为涉及 IBD 病理生理学的重要因素受到关注。作为与 IBD 相关的既定细菌“肠型”的补充，我们在这里重点关注病毒。我们研究了正在接受生物治疗的 IBD 患者的肠道病毒组，以确定与 IBD 相关的病毒组构型的存在，并揭示这些构型如何与治疗成功相关。
对 181 名开始接受生物治疗的 IBD 患者的 432 份粪便样本进行病毒样颗粒富集，然后进行深度测序。冗余分析和 Dirichlet 多项混合分别用于确定病毒组组成的协变量，并将肠道病毒组浓缩成“病毒群落类型”。
根据无监督聚类，患者分为两种病毒群落类型。群落类型 CA 表现出低α多样性和高 Caudoviricetes [非 CrAss]噬菌体相对丰度，并与失调的 Bact2-肠型相关。群落类型 CrM 表现出高α多样性和高 Crassvirales 和 Malgrandaviricetes 噬菌体相对丰度。在干预后分析中，内镜结果与肠道病毒组组成相关。缓解的 UC 患者具有高比例的群落类型 CrM、高 Shannon 多样性和低溶原潜力。干预前分析还鉴定了与治疗成功相关的五个新噬菌体。
本研究提出了两种可能参与 IBD 病理生理学的肠道病毒组构型。有趣的是，这些病毒构型进一步与治疗成功相关，表明可能具有临床相关性。
