Oral inoculation ofexacerbates ulcerative colitis via the secretion of virulence adhesin FadA.

Abstract

(), an anaerobic resident of the oral cavity, is increasingly recognized as a contributing factor to ulcerative colitis (UC). The adhesive properties ofare mediated by its key virulence protein, FadA adhesin. However, further investigations are needed to understand the pathogenic mechanisms of this oral pathogen in UC. The present study aimed to explore the role of the FadA adhesin in the colonization and invasion of oralin dextran sulphate sodium (DSS)-induced colitis mice via molecular techniques. In this study, we found that oral inoculation ofstrain carrying the FadA adhesin further exacerbated DSS-induced colitis, leading to elevated alveolar bone loss, disease severity, and mortality. Additionally, CDH1 gene knockout mice treated with DSS presented increases in body weight and alveolar bone density, as well as a reduction in disease severity. Furthermore, FadA adhesin adhered to its mucosal receptor E-cadherin, leading to the phosphorylation of β-catenin and the degradation of IκBα, the activation of the NF-κB signalling pathway and the upregulation of downstream cytokines. In conclusion, this research revealed that oral inoculation withfacilitates experimental colitis via the secretion of the virulence adhesin FadA. Targeting the oral pathogenand its virulence factor FadA may represent a promising therapeutic approach for a portion of UC patients.