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

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)).