Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.

粪便菌群移植治疗艰难梭菌感染期间的噬菌体转移与治疗结果的相关性

Abstract

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.

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）。研究显示虽经FMT治疗后细菌定植， 但得到CDI病毒变化的数据较少。我们研究了经治疗CDI后肠道病毒体的变化以及病毒转移与CDI患者临床结果之间的关联。

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.

设计：对来自24名CDI受试者和20名健康对照的粪便样品进行病毒样颗粒剂的超深宏基因组测序和细菌16S rRNA测序。我们纵向评估了用FMT治疗的9名CDI受试者和用万古霉素治疗的5名CDI受试者的病菌微生物组变化。评估肠道病毒体变化与治疗效果的相关性。

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.

结果：与健康的家庭对照相比，患有CDI受试者的有尾噬菌体丰度更高和种类较少。在CDI中观察到变形菌，放线菌和有尾噬菌体类之间的显著相关性。经FMT处理导致CDI中有尾噬菌体丰度显著降低。当来自供体的有尾噬菌体contigs占受体肠道病菌的大部分时，观察到FMT后得到治愈（p = 0.024）。在治疗应答者中，FMT与病毒体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。

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.

结论：在初步研究中，CDI的特征在于肠道病菌的生态失调。FMT的治疗效果与受体中来自供体的有尾噬菌体的高定殖水平相关。有尾噬菌体可能在FMT治疗CDI效果中发挥作用。

病毒转移（viral transfer）是一种基因剪接，它以病毒作为所需基因序列的载体。

read：测序时，产生的较短的原始序列叫read；

contigs：有多个reads通过片段的重叠，组装成一个更大的read，称为contigs；

scaffold：多个contigs通过片段的重叠拼接成更长的scaffold。

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