Unveiling the IL-1β/CXCL2 axis: a shared therapeutic target in periodontitis and inflammatory bowel disease.

Abstract

BACKGROUND: Periodontitis is clinically associated with inflammatory bowel disease (IBD), yet the shared cellular and molecular programs underpinning this oral-gut inflammatory link remain incompletely defined. METHODS: We integrated bulk gingival transcriptomes from two periodontitis cohorts (GSE16134 and GSE10334) with single-cell RNA-seq data from IBD patients (51,322 cells, 18 samples). After standard quality control and batch-aware integration, we performed pseudobulk differential expression gene (DEG) analysis at the patient level to identify IBD-associated genes and intersected these with periodontitis-consensus DEGs to derive shared signatures. Cell-cell communication networks were inferred using CellChat, and gene set enrichment analysis were conducted to delineated inflammatory signaling. Myeloid subpopulations further resolved to characterize disease-associated functional states. Key findings were assessed in a dual-inflammation rodent model by immunohistochemistry. RESULTS: We identified 188 common DEGs across the two periodontitis cohorts and 66 genes shared in IBD, which were predominantly enriched in immune compartments and motivated a focused analysis of myeloid cells. Communication analysis revealed extensive network remodeling in IBD, with myeloid populations acting as major signaling hubs. Myeloid subclustering highlighted inflammatory and chemokine-related states characterized by highexpression. Among chemokines,was prioritized because it showed consistent upregulation across bulk periodontitis transcriptomes and IBD myeloid states, and it aligned with prominent IL-1β-chemokine signaling routes inferred from intercellular communication., IL-1β and CXCL2 signals were increased in the dual-inflammation model, supporting cross-disease consistency of this axis. CONCLUSIONS: Our integrative analyses identify a shared, myeloid-centered IL-1β/chemokine inflammatory program across periodontitis and IBD, which may contribute to the oral-gut inflammatory axis. The IL1β-CXCL2 pathway represents a potentially targetable signaling module, although functional blockade studies are required to establish therapeutic causality.