Sleep disturbance is tightly linked to immune dysregulation and the gut–brain axis. Emerging evidence suggests aging may exacerbate this connection through immunosenescence and gut microbiota alterations. However, the molecular connection between Helicobacter pylori infection and insomnia remains poorly characterized.

We identified 147 common differentially expressed genes (DEGs) enriched in immune and inflammatory pathways. Central to the protein–protein interaction (PPI) network were seven hub genes, primarily MHC class II components (HLA-DPB1, HLA-DRB1, and CD74) that contribute significantly to immunological aging processes. Immune infiltration showed elevated CD8+ T cells and T helper cells in insomnia, consistent with aging-associated immune profiles. A candidate competing endogenous RNA (ceRNA) network comprising 7 lncRNAs, 8 miRNAs, and 8 mRNAs was predicted.

Our findings highlight an age-relevant immuno-inflammatory link between H. pylori infection and insomnia and propose a testable ceRNA network, suggesting potential mechanisms for the increased insomnia prevalence in aging populations with chronic H. pylori infection.

We analyzed public gene expression datasets (GSE60427 for H. pylori infection and GSE208668 for insomnia) to identify shared DEGs using the limma package. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, PPI analysis, immune cell infiltration, and a lncRNA–miRNA–mRNA ceRNA network predictions were performed.