Characterising the vaginal microbiome using state-of-the-art metagenomics among women in the general British population to inform sexual and reproduct

微生物组代表微生物的集合及其在特定环境中的活动场所。大部分关于人类微生物组的研究都集中在胃肠道、口腔和皮肤微生物组上。阴道微生物群在妇女性健康和生殖健康中发挥着重要作用，但人们对它的关注较少。阴道生态失调，包括阴道微生物群的高度物种多样性取代乳酸杆菌物种，与大多数妇女健康状况不佳的风险增加有关。这些疾病包括细菌性阴道病（BV）、念珠菌病、尿路感染（UTI）和盆腔炎，以及获得性传播感染（STIs）（包括艾滋病毒）的较高风险，以及不利的生殖健康结果，包括不孕症、异位妊娠和早产。根据社会人口学特征（如种族和年龄）、社会实践和行为（如吸烟、最近的性伴侣）以及临床特征（如性传播感染、抗生素使用），阴道微生物组的组成存在差异。然而，研究在很大程度上仅限于方便的样本，这些样本来自到卫生服务机构就诊的妇女，或通过在线/印刷广告招募的妇女，因此容易产生选择偏见。此外，样本量通常较小，限制了统计效力，并且缺乏全面的元数据，限制了在调查微生物组组成和宿主特征之间的关联时对潜在混杂因素的调整。最值得注意的是，以前没有研究使用来自一般人群的代表性样本的数据来描述阴道微生物组。全国性态度和生活方式调查（Natsal）是在英国每十年进行一次的横断面研究，它代表了一般人群。Natsal-4（田野调查2022-24）是第一个对大部分成年期（16-59岁）顺性女性自收集的阴道拭子样本进行宏基因组测序的Natsal调查。在Natsal-4中收集了大量具有代表性的阴道拭子样本（预计约1000个拭子），加上详细的社会人口统计学、行为和临床数据，以及使用歧视性的最先进的宏基因组测序方法，将使我们能够比迄今为止更详细地描述整个生命过程中的阴道微生物组特征，并调查相关因素。该项目旨在通过社会人口学、行为和临床特征来描述英国普通人口中女性阴道微生物群的特征，以确定可能影响其组成的因素。目的是研究阴道微生物组在以下情况下的变化：主要社会人口学特征（例如，按不同种族和其他社会人口学特征划分的整个生命历程，包括性前经历、生育年龄、围绝经期和绝经期）2 .性行为、性实践和性伴侣类型（如伴侣人数、性行为类型、伴侣性别）。报告的外阴阴道症状和发病率（例如，细菌性阴道炎、念珠菌病、尿路感染，可能与处方数据等其他数据集有关联）3。性传播感染（诊断和报告）干预措施（报告的抗生素使用情况、使用的避孕措施类型（避孕套、宫内节育器、口服避孕药））。

The microbiome represents the collection of microorganisms and their theatre of activity in a particular environment. Much of the research into the human microbiome has focused on the gastrointestinal, oral, and skin microbiomes. Less attention has been accorded to the vaginal microbiome, which plays an important role in women's sexual and reproductive health. Vaginal dysbiosis, including replacement of Lactobacillus species by a high species diversity of the vaginal microbiome, has been associated with increased risk of poor health outcomes among most women. These range from bacterial vaginosis (BV), candidiasis, urinary tract infection (UTI) and pelvic inflammatory disease, to a higher risk of acquiring sexually transmitted infections (STIs), including HIV, as well as adverse reproductive health outcomes, including infertility, ectopic pregnancy, and preterm birth. Differences in the composition of the vaginal microbiome by sociodemographic characteristics (e.g., ethnicity and age), by social practices and behaviours (e.g., smoking, recent sex partner/s), and by clinical characteristics (e.g., STI presence, antibiotic use) have been described. However, studies have largely been limited to convenience samples from women presenting to health services, or who were recruited via online/print advertisements, and thereby prone to selection bias. Moreover, sample sizes were generally small, limiting statistical power, and lacked comprehensive metadata, limiting adjustment for potential confounders when investigating associations between the microbiome composition and host characteristics. Most notably, no previous research has characterised the vaginal microbiome using data from a representative sample of the general population. The National Surveys of Sexual Attitudes and Lifestyles (Natsal) are cross-sectional studies occurring decennially in Britain, which are representative of the general population. Natsal-4 (fieldwork 2022-24) is the first Natsal survey to carry out metagenomic sequencing on self-collected vaginal swab samples from cisgender women across most of the adult life course (16-59-year-olds). The large and representative sample of participants in Natsal-4 with vaginal swab samples collected (~1,000 swabs predicted), together with detailed sociodemographic, behavioural, and clinical data, as well as the use of discriminatory state-of-the-art metagenomic sequencing methods will allow for a more detailed characterisation of the vaginal microbiome across the life course and investigation of associated factors than has been possible to date.This project aims to characterise the vaginal microbiome among women in the general British population, by sociodemographic, behavioural, and clinical characteristics, to identify factors that might influence its composition. Objectives are to investigate how the vaginal microbiome varies by:1. Key sociodemographic characteristics (e.g., over the life course, including pre sexual experience, reproductive years, perimenopause, and menopause, by different ethnicities, and by other sociodemographic characteristics)2. Sexual behaviours, sexual practices, and types of sexual partnerships (e.g., number of partners, type of sex, gender of partners)3. Reported vulvovaginal symptoms and morbidity (e.g., BV, candidiasis, UTIs, with potential for linkage to other datasets such as prescription data)4. STIs (diagnosed and reported)5. Interventions (reported antibiotic use, types of contraception used (condoms, intrauterine devices, oral contraceptives)).