AUTHOR=Zeng Huiqiong , Zhou Kaixia , Zhuang Yu , Li Aidong , Luo Baiwei , Zhang Ye 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=15

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1273104

DOI=10.3389/fnagi.2023.1273104

ISSN=1663-4365

ABSTRACT=<sec id="sec1"><title>Purpose</title><p>Studies have shown a close relationship between gut microbiota (GM) and Alzheimer’s disease (AD). However, the causal relationship between them remains unclear.</p></sec><sec id="sec2"><title>Methods</title><p>We 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 (<italic>p</italic> &lt; 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.</p></sec><sec id="sec3"><title>Results</title><p>IVW analysis revealed significant correlations between certain microbial taxa and the risk of AD. Higher abundances of <italic>Actinobacteria</italic> at the class level, phylum. <italic>Actinobacteria</italic>, class. <italic>Deltaproteobacteria</italic>, order. <italic>Desulfovibrionales</italic>, genus. <italic>Oscillospira</italic>, and genus. <italic>Ruminococcaceae</italic> UCG004 (<italic>p</italic> &lt; 0.048) was found to be positively associated with an elevated risk of AD. However, within the genus-level taxa, <italic>Ruminococcus1</italic> (<italic>p</italic> = 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 <italic>Q</italic> 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.</p></sec><sec id="sec4"><title>Conclusion</title><p>This 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.</p></sec>