Ren ZL, Zhou HH, Chen CP, He H, Wang DL, Liu Z. Causal relationships between gut microbiota and dementia: A two-sample, bidirectional, Mendelian randomization study. World J Clin Cases 2024; 12(16): 2780-2788 [PMID: 38899286 DOI: 10.12998/wjcc.v12.i16.2780]
Corresponding Author of This Article
Zhou Liu, MD, Associate Chief Physician, Deputy Director, Department of Neurology, The Affiliated Hospital of Guangdong Medical University, No. 57 People's Avenue South, Zhanjiang 524000, Guangdong Province, China. liuzhou@gdmu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Zhao-Lin Ren, Hai-Hong Zhou, Hao He, Zhou Liu, Department of Neurology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong Province, China
Chu-Pei Chen, Department of Clinical Medicine, Guangdong Medical University, Zhanjiang 524000, Guangdong Province, China
Duo-Lao Wang, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool L693BX, United Kingdom
Co-corresponding authors: Duo-Lao Wang and Zhou Liu.
Author contributions: Ren ZL designed the study, analyzed and interpreted the data, and drafted the manuscript; Zhou HH, Chen CP and He H helped with data analysis and manuscript revision; Liu Z and Wang DL performed critical reading and editing of the manuscript; All authors made contributions to the article and approved the final version for submission.
Supported byScience and Technology Planning Project of Zhanjiang, No. 2021A05071; Clinic and Basic Research Project of Guangdong Medical University, No. 4SG23284G; and The Affiliated Hospital of Guangdong Medical University, No. LCYJ2018A003.
Institutional review board statement: This study utilized publicly available GWAS summary data and published trial data. This work did not involve the collection of original data, thus precluding the need for ethics committee approval.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zhou Liu, MD, Associate Chief Physician, Deputy Director, Department of Neurology, The Affiliated Hospital of Guangdong Medical University, No. 57 People's Avenue South, Zhanjiang 524000, Guangdong Province, China. liuzhou@gdmu.edu.cn
Received: January 7, 2024 Revised: March 19, 2024 Accepted: April 9, 2024 Published online: June 6, 2024 Processing time: 143 Days and 3.7 Hours
Abstract
BACKGROUND
Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia, including Alzheimer's dementia, vascular dementia, and dementia in other diseases classified elsewhere. However, the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain unclear.
AIM
To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization (MR) analysis.
METHODS
A bidirectional, two-sample, MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study (GWAS) summary data from the MiBioGen consortium alongside GWAS summary statistics for dementia and its subtypes from the FinnGen consortium. Instrumental variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the F-statistic. Five MR methods were employed, and the robustness of our findings was validated. To account for multiple comparisons, we applied the Bonferroni method for P-value adjustment.
RESULTS
We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes, potentially serving as risk or protective factors for the disease. In addition, reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its subtypes. An exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy. After applying correction for multiple testing, we observed that the order Bacillales (odds ratio: 0.830, 95% confidence interval: 0.740-0.932, P = 0.00155, Padjust = 0.0311) exhibited a strong association with Alzheimer’s disease-related dementia.
CONCLUSION
The results suggest that gut microbiota is causally associated with dementia. Our findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention.
Core Tip: We identified several gut microbiota taxa as being associated with the risk of or protection against dementia, including its subtypes. These gut microbiota also exhibited potential as therapeutic targets for the disease. Conversely, reverse Mendelian randomization analysis indicated that dementia or its subtypes also influenced the abundance of several gut bacteria, implying that these taxa may serve as biomarkers for assessing the occurrence and progression of dementia. This study offers novel insights into the mechanisms underlying the role of the gut microbiome in this disorder.
