Research Sarah Ahannach

Abstract

Human papillomavirus (HPV) is the underlying cause of most cervical cancers. This virus infects nearly all sexually active women at least once in their lifetime. Although most HPV infections are transient and resolve without long-term consequences, a subset persists, creating the foundation for malignant transformation. Yet, the mechanisms that determine whether an infection persists or clears remain poorly defined. This poses a significant challenge in the diagnosis of HPV infections, which often carries a considerable psychological burden for women due to anxiety about cancer risk and uncertainty around prognosis. While host immune responses are essential for viral clearance, growing evidence indicates that the vaginal microbiome plays a pivotal role in shaping these outcomes. Lactobacillus-dominated communities are associated with a lower risk of persistence, whereas diverse or dysbiotic microbiomes, enriched in taxa such as Gardnerella or Fannyhessea, correlate with chronic infection and progression to high-grade lesions. However, the causal pathways through which the microbiome influences HPV dynamics remain largely unexplored. This project aims to uncover the mechanistic basis of microbiome-driven HPV clearance, thereby positioning the microbiome as both a diagnostic and therapeutic target. First, we seek to go beyond descriptive associations and identify protective taxa that contribute to viral elimination. The vaginal microbiome of women with clearance versus persistent HPV infections will be characterised. Shotgun metagenomics will provide high-resolution profiles of microbial diversity and dominance patterns. This will give us an insight into microbial biomarkers for clearance and persistence of the infection, guiding the development of a predictive model to determine whether an infection is likely to resolve or persist. Next, host-virus-microbial functional interactions will be investigated by using metatranscriptomics. This will allow us to map the transcriptional activity of both host epithelial cells and the present bacteria during clearance versus persistence. Particular attention will be given to immune pathways such as type I and III interferon signalling, cytokine expression (e.g. IFN-γ, IL-17, IL-10), and epithelial barrier integrity, as well as bacterial metabolic pathways linked to lactic acid production and metabolite production. Correlating microbial activity with host gene expression will provide mechanistic insight into how beneficial strains promote an antiviral mucosal environment. The vaginal strains that are identified as protective will be isolated, sequenced, and functionally characterized. These isolates will then be tested in advanced HPV infection models, including HeLa cells infected with pseudoviruses, E6/E7-expressing cell systems, and 3D cervicovaginal tissue or organ-on-chip platforms to uncover the mechanisms linked to immune modulation, antiviral metabolite production, or epithelial adhesion. These models will enable mechanistic interrogation of how specific bacterial strains alter viral replication, immune signalling, and epithelial homeostasis in both acute and persistent infection contexts. By integrating clinical expertise, host transcriptomics, and mechanistic validation, this project moves beyond correlation to establish causal mechanisms in microbiome–HPV research. The expected outcomes include the identification of clinically relevant microbial and host biomarkers predictive of HPV clearance, characterisation of host-virus–microbiome pathways that regulate mucosal antiviral immunity, and mechanistic insights into viral clearance derived from testing bacterial strains in advanced 3D HPV infection models. Ultimately, this work will establish an actionable framework for how the vaginal microbiome modulates HPV infection, with implications for developing microbiome-based diagnostics and therapeutics that enhance natural clearance and prevent progression to cervical cancer.

Researcher(s)

• Promoter: Verhoeven Veronique
• Co-promoter: Ahannach Sarah
• Co-promoter: Lebeer Sarah

Research team(s)

• Primary and interdisciplinary care Antwerp (ELIZA)

Project type(s)

• Research Project

Abstract

The Isala citizen science initiative is the world's largest participatory research project focused on women's health and the vaginal microbiome. Through large-scale sampling and community engagement, Isala has built a biobank of over 10,000 vaginal samples and >3,000 microbial isolates. The program investigates associations between microbiota and factors such as age, menstrual hygiene, contraception, and cultural practices, and develops innovative tools for microbiome-based diagnostics and health empowerment.

Researcher(s)

• Promoter: Ahannach Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The Luna project aims to explore the impact of menstrual hygiene products on the vulvar and vaginal microbiomes, a crucial and understudied aspect of menstrual health. Recognizing menstrual hygiene access as a human right, the initiative addresses significant gaps in understanding how various products might influence women's health, including risks such as Menstrual Toxic Shock Syndrome (mTSS). By leveraging a substantial biobank from the Isala project, Luna engages a cohort of 100 healthy menstruators aged 18-40 and evaluates microbiome effects over five menstrual cycles using both traditional and sustainable hygiene products. The study distinguishes itself by incorporating vulvar microbiome analysis, an area often overlooked in previous research that primarily focused on vaginal health. The project hypothesizes that menstrual hygiene products affect the urogenital ecosystem in ways beyond mTSS. Using advanced sequencing techniques alongside comprehensive surveys, Luna seeks to understand women's beliefs and perceptions regarding menstrual hygiene products. The longitudinal intervention study will analyze microbiome shifts over time across five menstrual cycles with different products, identifying connections to vulvovaginal symptoms. Ultimately, the Luna project aspires to translate findings into actionable insights, driving stakeholder engagement in policy-making and industry standards, while contributing to Sustainable Development Goals related to health and gender equality. With this BOF SRG, it aims to generate critical evidence that enhances menstrual health practices and empowers women to make informed choices regarding their reproductive health.

Researcher(s)

• Promoter: Ahannach Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Violence against women is an urgent global problem, as over one third of women worldwide has been victim of physical and/or sexual violence in their lifetime. And remarkably, only 25% of reported rape cases in Europe ultimately lead to a conviction, often due to the difficulty of providing evidence. Recent advances in microbial profiling have uncovered that each individual is home to complex microbial communities. These communities inhabit all surfaces of the human body (for example, orogastrointestinal tract, respiratory tract, urogenital tract, skin) and collectively represent the human microbiota, with their microbial DNA signatures forming the microbiome. Recent research suggests that the microbiome could greatly aid forensic casework as a promising tool to strengthen traditional forensic investigative methods and fill related knowledge gaps. Large-scale microbiome studies indicate that microbial fingerprinting can assist forensics in areas such as trace evidence, source tracking, geolocation, and circumstances of death. The goal of this project to investigate the potential of the female microbiome as an additional forensic tool in criminal investigations, with a focus on sexual assault cases. We aim to do this in three ways. First, we want to establish a large, curated dataset with 16S rRNA and (shallow) shotgun sequences of vaginal, skin and saliva samples. Second, we want to re-create forensically relevant samples (i.e., mock crime scenes) such as mixtures, long-term stored traces, sexual intercourse samples, etc. in a controlled environment. These samples will carry a crucial added-value to the curated dataset that will serve as a training set. At last, we aim to validate our hypotheses and the developed classification model in collaboration with the Institute of Forensic Medicine at University of Zurich. This tool will be able: i) to predict traces of body sites/fluids taken from other body sites/fluids or, in other words, to discriminate "pure" from mixture samples; ii) to predict from a vaginal sample whether intercourse has recently taken place. For the validation of this model, we aim to sequence the microbiome of at least 100 vaginal, skin and saliva samples from real-life sexual violence crimes that occurred in the district of Antwerp. This is not only highly favorable but also necessary to have a robust dataset to test out hypotheses and which can function as a solid test set. Being able to sequence 100 sexual assault samples would give as a strong chance to validate our hypotheses and classification model.

Researcher(s)

• Promoter: Ahannach Sarah

Research team(s)

Project type(s)

• Research Project

Abstract

In this project, we aim to use a combination of bio-informatic and experimental approaches to explore important aspects of niche flexibility and functions of Lactobacillus strains, using the Lactobacillus casei/rhamnosus group as case study. Here, niche-adaptation of these bacteria will be explored for rather unexplored niches, namely fermented vegetables (carrots), the human vagina and the human respiratory tract, starting from isolates, which are in- house available through previous projects. Experiments will include niche-swap experiments, experimental evolution and functional analyses by constructed knock-out mutants. Special attention in this PhD project will be directed towards the role of adhesion in niche colonization. In previous research, a new type of fimbriae was found in L. casei and this will be further explored and molecularly characterized in this PhD project.

Researcher(s)

• Promoter: Lebeer Sarah
• Fellow: Ahannach Sarah

Research team(s)

Project website

Project type(s)

• Research Project