Exploring the common mechanism of vascular dementia and inflammatory bowel disease: a bioinformatics-based study

Front Immunol. 2024 Apr 25:15:1347415. doi: 10.3389/fimmu.2024.1347415. eCollection 2024.

Abstract

Objective: Emerging evidence has shown that gut diseases can regulate the development and function of the immune, metabolic, and nervous systems through dynamic bidirectional communication on the brain-gut axis. However, the specific mechanism of intestinal diseases and vascular dementia (VD) remains unclear. We designed this study especially, to further clarify the connection between VD and inflammatory bowel disease (IBD) from bioinformatics analyses.

Methods: We downloaded Gene expression profiles for VD (GSE122063) and IBD (GSE47908, GSE179285) from the Gene Expression Omnibus (GEO) database. Then individual Gene Set Enrichment Analysis (GSEA) was used to confirm the connection between the two diseases respectively. The common differentially expressed genes (coDEGs) were identified, and the STRING database together with Cytoscape software were used to construct protein-protein interaction (PPI) network and core functional modules. We identified the hub genes by using the Cytohubba plugin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to identify pathways of coDEGs and hub genes. Subsequently, receiver operating characteristic (ROC) analysis was used to identify the diagnostic ability of these hub genes, and a training dataset was used to verify the expression levels of the hub genes. An alternative single-sample gene set enrichment (ssGSEA) algorithm was used to analyze immune cell infiltration between coDEGs and immune cells. Finally, the correlation between hub genes and immune cells was analyzed.

Results: We screened 167 coDEGs. The main articles of coDEGs enrichment analysis focused on immune function. 8 shared hub genes were identified, including PTPRC, ITGB2, CYBB, IL1B, TLR2, CASP1, IL10RA, and BTK. The functional categories of hub genes enrichment analysis were mainly involved in the regulation of immune function and neuroinflammatory response. Compared to the healthy controls, abnormal infiltration of immune cells was found in VD and IBD. We also found the correlation between 8 shared hub genes and immune cells.

Conclusions: This study suggests that IBD may be a new risk factor for VD. The 8 hub genes may predict the IBD complicated with VD. Immune-related coDEGS may be related to their association, which requires further research to prove.

Keywords: biomarkers; immune cells infiltration; inflammatory bowel disease; pathogenesis; the brain-gut axis; vascular dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology* / methods
  • Databases, Genetic
  • Dementia, Vascular* / genetics
  • Dementia, Vascular* / immunology
  • Gene Expression Profiling*
  • Gene Ontology
  • Gene Regulatory Networks*
  • Humans
  • Inflammatory Bowel Diseases* / genetics
  • Inflammatory Bowel Diseases* / immunology
  • Protein Interaction Maps*
  • Transcriptome

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the National Natural Science Foundation of China (No. 8187140739).