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

Huiqiong Zeng; Kaixia Zhou; Yu Zhuang; Aidong Li; Baiwei Luo; Ye Zhang

doi:10.3389/fnagi.2023.1273104

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

Front Aging Neurosci. 2023 Oct 16:15:1273104. doi: 10.3389/fnagi.2023.1273104. eCollection 2023.

Authors

Huiqiong Zeng¹, Kaixia Zhou², Yu Zhuang³, Aidong Li⁴, Baiwei Luo⁵, Ye Zhang⁶

Affiliations

¹ Department of Rheumatology, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, Guangdong, China.
² Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, China.
³ Department of Rheumatology and Immunology, Huizhou Central People's Hospital, Huizhou, Guangdong, China.
⁴ Department of Rehabilitation, The Second People's Hospital of Futian District, Shenzhen, Guangdong, China.
⁵ Department of Rheumatology and Immunology, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, China.
⁶ Department of Traditional Chinese Medicine, Women and Children Health Institute Futian Shenzhen, Shenzhen, China.

Abstract

Purpose: Studies have shown a close relationship between gut microbiota (GM) and Alzheimer's disease (AD). However, the causal relationship between them remains unclear.

Methods: 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 (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.

Results: IVW 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.

Conclusion: 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.

Keywords: Alzheimer’s disease; Mendelian randomization; causal relationship; genetic analysis; gut microbiota.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financially supported in part by research grants from the Sanming Project of Medicine in Shenzhen (SZSM201602087), Shenzhen Science and Technology Project (JCYJ20180302145033769), and Futian Healthcare Research Project (FTWS2021062).