Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysis

Abstract

PurposeStudies have shown a close relationship between gut microbiota (GM) and Alzheimer’s disease (AD). However, the causal relationship between them remains unclear.MethodsWe conducted a genome-wide association study (GWAS) using publicly available summary statistics data for GM and AD. We extracted independent genetic loci significantly associated with GM relative abundances as instrumental variables based on predefined thresholds (p < 1*e−5). The inverse variance-weighted (IVW) method was primarily used for causal relationship assessment. Additional analyses, including MR-Egger, weighted median, simple mode, and weighted mode, were performed as supplementary analyses.ResultsIVW analysis revealed significant correlations between certain microbial taxa and the risk of AD. Higher abundances of Actinobacteria at the class level, phylum. Actinobacteria, class. Deltaproteobacteria, order. Desulfovibrionales, genus. Oscillospira, and genus. Ruminococcaceae UCG004 (p < 0.048) was found to be positively associated with an elevated risk of AD. However, within the genus-level taxa, Ruminococcus1 (p = 0.030) demonstrated a protective effect on lowering the risk of AD. In addition, to ensure the robustness of the findings, we employed Cochrane’s Q test and leave-one-out analysis for quality assessment, while the stability and reliability of the results were validated through MR-Egger intercept test, MR-PRESSO global test, and sensitivity analysis.ConclusionThis study provided a comprehensive analysis of the causal relationship between 211 GM taxa and AD. It discerned distinct GM taxa linked to the susceptibility of AD, thereby providing novel perspectives on the genetic mechanisms governing AD via the GM. Additionally, these discoveries held promise as valuable biomarkers, enabling the identification of potential therapeutic targets and guiding forthcoming AD investigations.

16S rRNA gene amplicon-based gut microbiome signature in cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: A prospective nested case-control pilot study

“…Gut-microbiota-brain axis (GMBA) is a bidirectional route of signaling between the digestive tract and central nervous system (CNS) that modulates health and disease and was shown to play a role in a plethora of neurological disorders such as ischemic stroke, multiple sclerosis, Alzheimer's disease, or others [2][3][4] . Moreover, our group recently published a systematic review with a narrative synthesis which highlighted the role of gut microbiota in growth and rupture of intracranial aneurysms 5 .…”

Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites

“…Thanks to large-scale GWAS of gut microbiotas in different diseases, MR has been widely used to study disease pathogenesis. Indeed, several studies using MR have now established that the gut microbiota is strongly associated with several neurological diseases including Alzheimer’s disease ( Zeng et al, 2023 ), major depressive disorder ( Chen M. et al, 2022 ), schizophrenia ( Cheng et al, 2023 ), and insomnia ( Li et al, 2023 ).…”

Association between gut microbiota and Hirschsprung disease: a bidirectional two-sample Mendelian randomization study

“…MR follows Mendelian’s second law and relies on independent random assignment of genetic variants during meiosis to achieve randomization effects similar to randomized controlled trials (RCTs), which can effectively overcome the confounding factors ( Ma et al, 2023 ; Vincent et al, 2023 ; Yan et al, 2023 ; Zanoaga et al, 2023 ). MR has been widely used to analyze the causal relationship between GM and spinal arthropathy ( Lai et al, 2023 ), ophthalmic disease ( Li and Lu, 2023 ), tumors ( Jiang et al, 2023 ), psychiatric disorders ( Zeng et al, 2023 ), and circulatory system disease ( Dai et al, 2023 ). However, the relationship between GM and HSCR has rarely been studied based on MR methods.…”