Objective Faecal microbiota transplantation (FMT) is effective for the treatment of recurrent Clostridium difficile infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI. Design Ultra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on stool samples from 24 subjects with CDI and 20 healthy controls. We longitudinally assessed the virome and bacterial microbiome changes in nine CDI subjects treated with FMT and five treated with vancomycin. Enteric virome alterations were assessed in association with treatment response. Results Subjects with CDI demonstrated a significantly higher abundance of bacteriophage Caudovirales and a lower Caudovirales diversity, richness and evenness compared with healthy household controls. Significant correlations were observed between bacterial families Proteobacteria, Actinobacteria and Caudovirales taxa in CDI. FMT treatment resulted in a significant decrease in the abundance of Caudovirales in CDI. Cure after FMT was observed when donor-derived Caudovirales contigs occupied a larger fraction of the enteric virome in the recipients (p=0.024). In treatment responders, FMT was associated with alterations in the virome and the bacterial microbiome, while vancomycin treatment led to alterations in the bacterial community alone. Conclusions In a preliminary study, CDI is characterised by enteric virome dysbiosis. Treatment response in FMT was associated with a high colonisation level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI. Trial registration number NCT02570477

中文翻译：

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艰难梭菌感染粪便微生物群移植过程中的噬菌体转移与治疗结果相关

目的粪便微生物群移植（FMT）可有效治疗复发性艰难梭菌感染（CDI）。研究表明 FMT 后细菌定植，但 CDI 中病毒改变的数据很少。我们调查了 CDI 肠道病毒组的改变以及病毒转移与 CDI 患者临床结果之间的关联。设计 对来自 24 名患有 CDI 的受试者和 20 名健康对照者的粪便样本进行了病毒样颗粒制剂的超深度宏基因组测序和细菌 16S rRNA 测序。我们纵向评估了九名接受 FMT 治疗的 CDI 受试者和五名接受万古霉素治疗的 CDI 受试者的病毒组和细菌微生物组变化。评估肠道病毒组改变与治疗反应的相关性。结果与健康的家庭对照相比，CDI 受试者表现出显着更高的噬菌体尾状病毒的丰度和较低的尾状病毒的多样性、丰富度和均匀度。在 CDI 中观察到细菌家族 Proteobacteria、Actinobacteria 和 Caudovirales 分类群之间的显着相关性。FMT 处理导致 CDI 中 Caudovirales 的丰度显着下降。当供体来源的尾状病毒重叠群占据受体肠道病毒组的大部分时，观察到 FMT 后的治愈 (p = 0.024)。在治疗应答者中，FMT 与病毒组和细菌微生物组的改变有关，而万古霉素治疗仅导致细菌群落的改变。结论 在初步研究中，CDI 的特征是肠道病毒群失调。FMT 中的治疗反应与受体中供体来源的尾状病毒分类群的高定植水平相关。Caudovirales 噬菌体可能在 FMT 在 CDI 中发挥作用。试验注册号 NCT02570477