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Periodontitis (PD) and ulcerative colitis (UC) are two common chronic inflammatory diseases increasingly connected via the "oral-gut axis," yet their shared molecular mechanisms remain unclear. Oxidative stress, driven by excessive reactive oxygen species (ROS), represents a key pathogenic mechanism common to both PD and UC. In this study, we integrated transcriptomic datasets from patients with PD and UC to identify oxidative stress-related genes underlying their comorbidity. By combining weighted gene co-expression network analysis (WGCNA), machine learning, and single-cell RNA sequencing, we identified and validated a set of comorbidity-associated diagnostic biomarkers: CXCL1, XBP1, CD93, FYN, SELP, and CXCR4. These genes demonstrated high diagnostic accuracy across independent datasets, and gene set enrichment analysis (GSEA) revealed their involvement in inflammatory and immune-related pathways. Single-cell analysis further demonstrated endothelial-specific co-expression of SELP and CD93, highlighting their potential roles in intercellular communication and chronic inflammation. Moreover, molecular docking identified candidate therapeutic compounds with strong binding affinities for these targets. Collectively, our findings elucidate shared oxidative stress-driven mechanisms linking PD and UC and propose novel biomarkers and therapeutic targets for these interconnected diseases.
Wang et al. (Fri,) studied this question.