Female-specific health conditions are underrepresented in research. The taboo felt by women to talk about intimate wellbeing is fed by this gender gap in scientific knowledge. This project aims to meet these needs by studying one of the most prevalent female-specific infections, vulvovaginal candidiasis (VVC), and paving the way towards its efficient diagnosis and treatment. About 70% of women worldwide suffer from vaginal candidiasis at least once in their life. An episode of this fungal infection is accompanied by a burning sensation, pain, and reduced mental well-being. Some women (about 5%) encounter such infections at least four times a year, referring to recurrent(R) VVC. The design of efficient diagnostic and therapeutic strategies for (R)VVC is hindered by a knowledge gap surrounding vaginal health. To meet the absolute need for more information, this project will characterize the role of the microbiome, metabolome, immune system, and pathogen characteristics in (R)VVC. To this end, a large sampling platform of women with/without VVC will be established in this project. The researchers will identify the most important and clinically relevant microorganisms, metabolites, and immune factors in VVC pathogenesis. VVC models will be developed and optimized, which will be used to validate the causality of the correlations identified in the cohort. Identified correlations will be proposed as biomarkers, and microbes, metabolites, and combinations, which effectively lower the pathogenicity of Candida species, will be further investigated for therapeutic potential. State-of-the-art tools and know-how of the researchers will allow the unraveling of the involved molecular pathways and elucidate how these can be exploited to optimize therapeutic efficacy. Finally, the knowledge gathered in this project will be used to improve the literacy of women on VVC using platforms established by the researchers as well as novel tools to be developed in this project.

Inclusion Criteria:

• Female
• Age: 18-50
• Premenopausal

Exclusion Criteria:

• Pregnancy
• Self-reported vaginal complaints (e.g. redness, itching, pain, burning sensation, abnormal vaginal discharge) in the past 12 months (only for healthy group)
• Use of antibiotics/antifungals in the month prior to sample collection (only for healthy group)

Patients with an active Candida infection will be recruited during consultations with the responsible physicians: Prof. Gilbert Donders and Prof. Veronique Verhoeven. This subgroup will include both acute vulvovaginal candidiasis patients (episodic VVC; n=100) and recurrent VVC patients (episodic RVVC; n=100). The active Candida infection of these patients will be confirmed through clinical evaluation. Furthermore, the responsible physicians will also recruit patients who have had at least three Candida infections in the past 12 months or have already been diagnosed with RVVC. This subgroup (non-episodic RVVC; n=100) does not have an active Candida infection at the time of sample collection. Additionally, a subgroup of healthy volunteers (n=200) will be recruited through various channels. These channels will also be used to reach VVC and RVVC patients and then refer them to Prof. Donders' team.

The metadata of participants in the study will be made available in a restricted access repository.

• For samples and data sharing, the researchers will work with the legal department to establish Material/Data Transfer Agreements.
• Sequencing data are available at the European Nucleotide Archive.
• Physical samples are their origin will be stored at the decentral hub of the Antwerp biobank.
• Concerning non-identifiable sample meta-data that the researchers will use in analysis and will later be published will be put available with access control via the European Genome-Phenome Archive (EGA), where data can be accessed as described upon agreeing to the harmonized Data Access Agreement (developed by the European Union standards for in silico models for personalized medicine EU-STANDS4PM, https://doi.org/10.6084/m9.figshare.23904300).

Following publication, the results associated with each study will also be deposited in the Dryad repository, where they will be preserved indefinitely. Sequences will be stored to ENA (public databases) and NCBI. All samples will be registered in the Biobank using the SLIMS system. A batch of the strains will be supplied to Sciensano to be stored in the BCCM collection.

A guide to data access on the EGA is available at https://ega-archive.org/access/data-access, and a data access request will be processed within 2-3 months, pending evaluation by the data access committee (existing of lab members involved in the study), and processing by the EGA.