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Project

Microbe-mucin isoform crosstalks mediating mucosal barrier function in the gastrointestinal tract versus vagina.

Upon gastrointestinal and reproductive homeostasis, there is an intimate crosstalk between mucins (MUCs) and the microbiome at the mucosal surface to maintain barrier integrity but a disbalance between both actors could dictate disease development, such as inflammatory bowel diseases (IBD) and aerobic vaginitis (AV). Indeed, thinning of the epithelium and aberrant MUC1 and MUC13 expression have been associated with barrier dysfunction in IBD. Also MUC1 seems to be increasingly expressed upon vaginal infection. Such defective mucus layer will thus allow microbiota to come in close contact with these mucins and co-elicit inflammation and mucosal damage. Nevertheless, which microbes interact with MUC1 and MUC13 in response to inflammation and dysbiosis and mediate barrier dysfunction in IBD and AV remains poorly understood. Therefore, we will first characterize microbiome diversity and function in IBD and AV using shotgun metagenomic sequencing. In parallel, we will also unravel the MUC1 and MUC13 mRNA isoform landscape using targeted isoform sequencing. Combining both sequencing data will allow to identify microbial-mucin isoform associations in IBD and AV. Finally, we will investigate the mechanism(s) by which abundant microbial species in IBD and AV interact with the aberrantly expressed MUC1 and MUC13 isoforms resulting in barrier dysfunction. To do so, bacterial mutant approaches and human epithelial organoid cultures established from IBD and AV samples will be used.
Date:1 Jan 2022 →  Today
Keywords:INFLAMMATORY BOWEL DISEASE, VAGINAL PATHOGENS, MUCIN, MICROBIOME
Disciplines:Gastro-enterology, Reproductive medicine, Inflammation, Microbiome, Cell signalling