Characterization of the vaginal DNA virome in health and dysbiosis: an opening study in patients with non-female factor infertility

Background Bacterial vaginosis (BV) is characterised by a reduction in Lactobacillus spp. abundance and increased abundance of facultative anaerobes, like Gardnerella vaginalis. BV aetiology is not fully understood, but bacteriophages could play a pivotal role causing perturbation of the vaginal bacterial community. Here we investigate the vaginal viral community, including bacteriophages, and its association to the bacterial community and BV-status.Methods Vaginal samples from 48 patients undergoing IVF treatment for non-female factor infertility were subjected to metagenomic sequencing of purified virus-like particles. The vaginal viral community was characterized and correlated with BV-status, bacterial community structure and presence of key vaginal bacterial species.Results The majority of identified vaginal viruses belonged to the class of double-stranded DNA bacteriophages, with eukaryotic viruses constituting 4% of total reads. Clear links between viral community composition and BV (q = 0.006, R = 0.26) as well as presence of L. crispatus (q = 0.001, R = 0.43), L. iners, Gardnerella vaginalis and Atopobium vaginae were found (q 0.15). Interestingly, also the eukaryotic viral community was correlated with BV-status (q = 0.018, R = 0.20).Conclusions The vaginal virome is clearly linked with bacterial community structure and BV-status.Clinical Trials Registration NCT02042352.

背景 细菌性阴道病（bacterial vaginosis, BV）以乳杆菌属（Lactobacillus spp.）丰度降低、兼性厌氧菌（如阴道加德纳菌（Gardnerella vaginalis））丰度升高为特征。目前细菌性阴道病的病因尚未完全明确，但噬菌体（bacteriophages）可能在扰乱阴道细菌群落过程中发挥关键作用。本研究旨在探究包括噬菌体在内的阴道病毒群落，及其与细菌群落结构、细菌性阴道病患病状态的关联。
方法 针对48名因非女性因素不孕症接受体外受精（in vitro fertilization, IVF）治疗的患者的阴道样本，本研究对纯化的病毒样颗粒（virus-like particles）开展宏基因组测序（metagenomic sequencing）。对阴道病毒群落进行特征解析，并将其与细菌性阴道病患病状态、细菌群落结构及关键阴道细菌物种的存在情况进行关联分析。
结果 本研究鉴定得到的多数阴道病毒属于双链DNA噬菌体，真核病毒占总测序读数的4%。研究发现病毒群落组成与细菌性阴道病（q=0.006, R=0.26）以及卷曲乳杆菌（L. crispatus）的存在（q=0.001, R=0.43）、惰性乳杆菌（L. iners）、阴道加德纳菌及阴道阿托波菌（Atopobium vaginae）均存在显著关联（q≤0.15）。值得注意的是，真核病毒群落同样与细菌性阴道病患病状态存在关联（q=0.018, R=0.20）。
结论 阴道病毒组（virome）与细菌群落结构及细菌性阴道病患病状态显著相关。
临床试验注册 NCT02042352。