Abstract
Background: Recent studies have highlighted the relationship between gut microbiome and Alzheimer’s disease (AD), revealing the ways of how gut microbial balance impacts conditions ranging from inflammatory bowel diseases to neurological disorders. The emerging field of the gut-brain-axis suggests production of microbial metabolites influences AD progression. However, there is limited understanding of molecular mechanisms involved in neurological disease when gut microbiome dysbiosis occurs. This study aimed to identify hub genes and pathways associated with gut microbiome dysbiosis 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 with p < 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 1715 genes in common. The top 10 common 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.
Conclusions: This study discovered that AD and inflammatory bowel disease share several differentially expressed genes in their pathogenesis mainly through positive regulation of leukocyte activation.
DOI
10.56808/2673-060X.5621
First Page
INTRODUCTION The gut-brain axis (GBA), a complex network of bi-directional communication between the central and the enteric nervous system, has been implicated in the plethora of health issues [1,2]. One approach to define gut health is as a state of physical and mental well-being characterized by the absence of gastrointestinal (GI) complaints and absence of indications or risks of bowel disease [3,4]. A balanced gut-brain axis is essential for fostering a symbiotic relationship with the gut microbiota, thereby facilitating crucial biological functions such as nutrient absorption, vitamin synthesis, and defense against pathogens [3,4]. However, this balance can be disturbed by many factors, including chronic stress, poor diet, or antibiotic misuse, leading to dysregulated state characterized by increased intestinal permeability and systemic inflammation [5,6]. This dysregulated stated will lead to the development of functional gastrointestinal diseases (FGID) [5,6]. FGIDs are a range of disorders such as irritable bowel syndrome, functional dyspepsia, or functional constipation are characterized by chronic or recurrent GI symptoms, which’s closely associated with GBA dysregulation [7]. Altered communications within this GBA can trigger a cascade of negative physiological responses such as abnormal gut motility, visceral hypersensitivity, and anomalous secretion patterns, in turn exacerbates the FGID’s symptoms [8]. Furthermore, several scientific studies suggest repercussions of this GBA dysregulation transcend the limitations of the gastrointestinal tract, having a substantial impact on brain health [8,9]. For instance, the persistent inflammation, byproduct of gut dysregulation, has been implicated in promoting neuroinflammation and neurodegeneration, affecting the structural and functional integrity of the brain [9]. Current research suggests that the disrupted gut microbiota can influence brain health through the productions of metabolites and endotoxins which are potentially amyloidogenic, a distinctive feature of Alzheimer disease (AD) [9-
Last Page
Legends for Figures Figure 1: Functional genomics analysis of the differentially expressed genes among Irritable Bowel Disease and Alzheimer’s Disease. Orange - biological processes; Green - cellular components; Blue - molecular function Figure 2: Co-expression network analysis of Irritable Bowel Disease and Alzheimer’s Disease associated with MHC Class II activity Figure 3: Regulation of leukocyte activation (blue nodes) signaling pathways involves in Irritable Bowel Disease and Alzheimer’s Disease pathogenesis Legends for Table Table 1: Gene interactions associated with positive regulation of cell activation
Recommended Citation
Rawi, Premaanand; Wong, Ying Pei; Tan, Ee Xion; and Ling, Anna Pick Kiong
()
"Elucidation of hub genes and pathway associated with Gut microbiome dysbiosis and Alzheimer’s disease via data analytic approaches,"
Chulalongkorn Medical Journal: Vol. 70:
Iss.
1, Article 1.
DOI: https://doi.org/10.56808/2673-060X.5621
Available at:
https://digital.car.chula.ac.th/clmjournal/vol70/iss1/1