Upregulation of MMP9 and ORM2 leading to increased neutrophil infiltration as a potential common mechanism in the development of IBD and MDD

Abstract

Major depressive disorder (MDD) is an emotional distinguished by core clinical symptoms such as low mood, diminished interest, lack of pleasure, reduced activity, and mental inhibition. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract with with an unknown etiology. Previous studies have indicated a positive association between MDD and IBD, although the specific underlying mechanism remains unclear. The objective of this research was to investigate shared differentially expressed genes (DEGs) common to MDD and IBD through bioinformatics analysis to elucidate the connection.The series matrix files of GSE3365 and GSE98793 were obtained from the NCBI GEO public database. The limma R package was utilized to identify DEGs common to MDD and IBD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation, protein–protein interaction analysis of the hub genes, weighted gene co-expression network analysis (WGCNA), correlation analysis of the hub genes with immune responses, and analysis of immune infiltrations were conducted. Gene set enrichment analysis was performed to elucidate the underlying pathogenesis. The intersection analysis identified 27 commonly upregulated genes and 13 downregulated genes. Subsequent GO and KEGG analyses revealed enrichment of infection-related signaling pathways among the DEGs. The integration of genes from the WGCNA module and differential genes resulted in the identification of eight commonly upregulated genes: PROS1, ORM2, SLP1, MMP9, CLEC5A, ARG1, OLR1, and EGF. Furthermore, immune infiltration analysis demonstrated an increase in neutrophil infiltration in both the MDD and IBD datasets. ORM2 and MMP9 were found to be correlated with neutrophil infiltration. These pivotal genes, associated with neutrophils and monocytes, play crucial roles in the pathophysiology of both conditions. Targeting ORM2 and MMP9 may hold promise as potential diagnostic and therapeutic strategies for managing the comorbidity of IBD and MDD.