Elucidation of hub genes and pathway associated with gut microbiome dysbiosis-linked irritable bowel disease and Alzheimer’s disease via data analytic approaches
Keywords:
Functional gastrointestinal disorders, gut-brain axis, gut dysregulation, inflammatory bowel diseaseAbstract
Background:Recent studies have highlighted the relationship between gut microbiome and Alzheimer’s disease (AD), revealing how gut microbial balance impacts conditions ranging from inflammatory bowel diseases to neurological disorders. The emerging field of the gut-brain axis suggests that the production of microbial metabolites influences AD progression. However, there is limited understanding of molecular mechanisms involved in neurological disease when gut microbiome dysbiosis occurs, especially in irritable bowel disease (IBD).
Objective:This study aimed to identify hub genes and pathways associated with gut microbiome dysbiosis in IBD and AD through data analytics approaches.
Methods:Public gene expression datasets on gut microbiome dysbiosis, and AD were obtained from the GEO and pre-processed for gene symbol annotation. Differentially expressed genes were identified withP< 0.05 and Log2FC≥1. Functional genomics analysis using DAVID (P< 0.05 and FDR < 0.05) was performed.Validated protein-protein interactions for differentially expressed genes (P< 0.05) were integrated into a comprehensive network using GeneMANIA and STRING.
Results:In total, AD and inflammatory bowel disease samples shared 1,715 genes in common. The top 10 common hub genes involved in positive regulation of leukocyte activation (CLEC7A, VNN1, SASH3, IL33,CD6, NFKBIZ, AIF1, ZBTB1, SIRBP1, LILRB1) were selected from the protein-protein interactions based on their top scores.
Conclusion:This study discovered that AD and IBD share hub genes in their pathogenesis mainly through positive regulation of leukocyte activation in the gut-brain axis that involves immune cell trafficking associated with inflammatory activation in IBD and microglia activation in AD, leading to neuroinflammation and neurodegeneration. The finding provides an insight into anti-neuroinflammatory therapeutic development targeting genes and molecular pathways within GBA.
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