Abstract
Background: Periodontitis is a common chronic inflammatory condition that begins with an imbalance in the subgingival microbial community, which, in turn, triggers a damaging host immune response. Although the role of bacteria is well known, the complete picture of the molecular drivers, especially the central genes and regulatory networks, remains incomplete. Objective: This study conducted an integrated bioinformatics analysis to identify principal regulator genes, associated pathways, and Gene Ontology (GO) terms involved in periodontitis. Methods: The transcriptomic dataset GSE223924 was reanalyzed, which included 10 healthy and 10 diseased gingival tissue samples. A differential expression analysis was performed with strict parameters (FDR < 0.01, |Log2FC| > 2). Subsequent analyses involved constructing a protein-protein interaction (PPI) network, a gene regulatory network via the STRING database and Cytoscape with iRegulon, and performing functional annotation using the g:Profiler database. Results: The results revealed 1,281 genes that were differentially expressed in periodontitis tissues. From a PPI network, we extracted 41 high-priority hub genes, with IL-6 consistently emerging as the most prominent. Investigation of transcriptional control identified NFKB1 as the primary regulator, controlling 15 of the hub genes. Pathway analysis further confirmed a strong enrichment of immune system functions, including "Cytokine-cytokine receptor interaction" and "Immune response". Conclusion: Our findings establish IL-6 and NFKB1 as central drivers within a dysregulated immune network in periodontitis. This molecular framework deepens our understanding of the disease's pathogenesis and provides a focused list of genes for further validation as potential therapeutic targets.