Dysbiosis of the gut microbiome may contribute to the pathogenesis of oral lichen planus through Treg dysregulation

Oral lichen planus (OLP) is a chronic inflammatory disorder with autoimmune features and malignant transformation risk, lacking a definitive treatment, with CD4⁺ T cells being pivotal in its pathogenesis. Dysbiosis, an imbalance in the microbiome, is linked to various autoimmune and inflammatory diseases, where CD4⁺ T cells play a significant role. Given these insights, the development of OLP might be influenced by dysbiosis. This study investigates the association between dysbiosis and CD4⁺ T cells in OLP. We collected stool and saliva samples from OLP patients, conducting 16S rRNA gene analysis and mass spectrometry, and assessed CD4⁺ T cell characteristics in lesions through multiplex immunofluorescence and single-cell RNA sequencing. Peripheral blood samples were subjected to flow cytometry and cell culture assays. Results showed extensive gut dysbiosis in OLP patients, notably a reduction in short-chain fatty acid (SCFA)-producing bacteria essential for regulatory T cell (Treg) differentiation. While various CD4⁺ T cell subsets, including Tregs, were present in tissues, these Tregs as unresponsive to specific antigens, showing reduced immunosuppressive molecule expression. The decline in SCFA-producing bacteria correlated with fewer activated Tregs in tissues and blood. These findings suggest that gut dysbiosis may contribute to OLP by impairing Treg regulation, influencing disease pathogenesis.