Unravelling the MAIT-Microbiome Axis in the Female Genital Tract: Microbial Vitamin B2 Metabolism as a driver of Mucosal Immunity and Barrier Protection
Abstract
Humans have evolved a unique symbiosis with lactobacilli in the female genital tract (FGT), where these microbes support reproductive health through lactic acid production and pathogen control. Yet how the vaginal immune system tolerates these beneficial microbes while remaining vigilant against pathogens remains largely unknown. MAIT cells sense microbial metabolites, including B vitamins via MR1, and their dual effector potential -tissue repair or antimicrobial activity- makes them prime candidates to mediate this balance. Their role in the FGT, however, is virtually unexplored. Building on our finding that vaginal lactobacilli produce vitamin B2 and activate circulating MAIT cells without inducing cytotoxicity, this project investigates whether lactobacilli can program MAIT cells to support epithelial barrier integrity. Using matched peripheral, menstrual, and endometrial samples (n = 1000), we will map FGT MAIT-cell diversity through high-dimensional phenotyping (CITE-seq). By leveraging vaginal microbiota members with varying virulence and their riboflavin-pathway mutants, we will dissect how commensals versus pathobionts differentially shape MAIT effector programs. Finally, a "vagina-on-a-chip" model will visualize MAIT migration, activation, and epithelial protection in real time. This work will establish the first mechanistic framework for MAIT–microbiome–epithelium crosstalk and provide a foundation for microbiome-based strategies to improve vaginal health.Researcher(s)
- Promoter: Lebeer Sarah
- Co-promoter: De Vos Winnok
- Fellow: Dricot Caroline
Research team(s)
Funding
- FWO
Project type(s)
- Research Project
Genetic screening, analysis and engineering of vitamin production in non-gut lactobacilli.
Abstract
Vitamin producing microorganisms are emerging as a natural, cost-effective and sustainable alternative to chemical vitamin production. To date, they have mainly been explored in the gut and fermented food, however, recently, the host group isolated several vaginal lactobacilli capable of vitamin B2 (over)production. Lactobacilli have a long history of safe use and are highly suitable for application as probiotics or for biofortification of foods, yet they are generally still applied as 'black boxes', without full understanding of the genes and molecules that drive their beneficial action. In this project, we will perform in silico and in vitro functional screening of the host group's large biobank of more than 1000 human bacterial isolates with the innovative goal to identify and characterize vitamin producing lactobacilli from untapped non-gut body niches (vagina, upper respiratory tract), and fermented foods. Next, to better understand and enhance the vitamin producing capacity of lactobacilli, untargeted and targeted genetic modification strategies will be implemented. A specific unique and challenging focus will be on the functionalization of the novel CRISPR-Cas9 based tool 'Prime editing' in lactobacilli for targeted genetic alterations leading to vitamin overproduction. Overproduction phenotypes, naturally isolated or resulting from genetic engineering approaches, can then be used in food/feed, as supplements and in human therapeutic applications.Researcher(s)
- Promoter: Lebeer Sarah
- Co-promoter: Spacova Irina
- Fellow: Dricot Caroline
Research team(s)
Funding
- FWO
- FWO
Project type(s)
- Research Project