Keeping infections at bay: interplay between microbes, mucins, and epithelium: Exploring the role of mucins and bacterial sialidases in bacterial vaginosis and intestinal homeostasis

Abstract

Mucosal surfaces in the human body are lined with epithelial cells and covered by a protective mucus layer, composed of both soluble and transmembrane mucins. Mucus is an important component of the innate immune system and is often referred to as the first line of defense. Disruption of epithelial barrier function can lead to several diseases, including inflammatory bowel disease (IBD) in the intestine and bacterial vaginosis (BV) in the FRT. Both conditions are characterized by increased inflammation and compromised barrier integrity. Moreover, specific bacteria in different microbial communities modulate mucin synthesis and O-glycan composition; conversely, the composition of mucin glycans modulates microbiota community composition. The research in this thesis advances our understanding of the role of specific vaginal bacteria, particularly Prevotella timonensis, in the development of bacterial vaginosis disease and the associated increased acquisition and risk of HIV-1 in women suffering from this condition. Additionally, we deepened our understanding of the functions of the transmembrane mucin MUC13 in the intestinal epithelium and identified commensal bacteria, specifically Bifidobacterium bifidum, that can modify MUC13 and other glycoproteins on intestinal cells and enhance epithelial barrier functions. These findings highlight the complex interactions between mucins and bacteria and their significant influence on mucosal health and disease. Our results may give new directions to the development of novel forms of prevention and therapy of mucosal health and disease.