Background

Periodontitis disease (PD) is associated with a systemic disorder of inflammatory bowel disease (IBD). The immune response is the common feature of the two conditions, but the more precise mechanisms remain unclear.

Methods

Differential expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were performed on PD and Crohn's disease (CD) data sets to identify crosstalk genes linking the two diseases. The proportions of infiltrating immune cells were calculated by using Single-sample Gene Set Enrichment Analysis. In addition, a data set of isolated neutrophils from the circulation was performed via WGCNA to obtain PD-related key modules. Then, single-cell gene set enrichment scores were computed for the key module and grouped neutrophils according to score order in the IBD scRNA-seq data set. Single-cell gene enrichment analysis was used to further explore the biological process of the neutrophils.

Results

A total of 13 crosstalk genes (IL1B, CSF3, CXCL1, CXCL6, FPR1, FCGR3B, SELE, MMP7, PROK2, SRGN, FCN1, TDO2 and CYP24A1) were identified via DEGs analysis and WGCNA by combining PD and CD data sets. The enrichment analysis showed that these genes were involved in interleukin-10 signaling and inflammatory response. The immune infiltration analysis showed a significant difference in the proportion of neutrophils in PD and CD compared with healthy patients. Neutrophils were scored based on the expression of a periodontitis-related gene set in the scRNA-seq data set of IBD. The enrichment analysis demonstrated that inflammatory response, TNFα signaling via NF-κB and interferon-gamma response were upregulated in the high-score group, which expressed more pro-inflammatory cytokines and chemokines compared with the low-score group.

Conclusions

This study reveals a previously unrecognized mechanism linking periodontitis and IBD through crosstalk genes and neutrophils, which provides a theoretical framework for future research.

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