Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysis
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 extract...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1273104/full |
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| author | Huiqiong Zeng Kaixia Zhou Yu Zhuang Aidong Li Baiwei Luo Ye Zhang |
| author_facet | Huiqiong Zeng Kaixia Zhou Yu Zhuang Aidong Li Baiwei Luo Ye Zhang |
| author_sort | Huiqiong Zeng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T18:18:28Z |
| format | Article |
| id | doaj.art-b1a9c73ab9c340738b449b1031688239 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-03-11T18:18:28Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-b1a9c73ab9c340738b449b10316882392023-10-16T05:08:13ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-10-011510.3389/fnagi.2023.12731041273104Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysisHuiqiong Zeng0Kaixia Zhou1Yu Zhuang2Aidong Li3Baiwei Luo4Ye Zhang5Department of Rheumatology, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, Guangdong, ChinaDepartment of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, ChinaDepartment of Rheumatology and Immunology, Huizhou Central People’s Hospital, Huizhou, Guangdong, ChinaDepartment of Rehabilitation, The Second People’s Hospital of Futian District, Shenzhen, Guangdong, ChinaDepartment of Rheumatology and Immunology, Yuebei People’s Hospital Affiliated to Shantou University Medical College, Shaoguan, Guangdong, ChinaDepartment of Traditional Chinese Medicine, Women and Children Health Institute Futian Shenzhen, Shenzhen, ChinaPurposeStudies 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.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1273104/fullMendelian randomizationgut microbiotaAlzheimer’s diseasecausal relationshipgenetic analysis |
| spellingShingle | Huiqiong Zeng Kaixia Zhou Yu Zhuang Aidong Li Baiwei Luo Ye Zhang Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysis Frontiers in Aging Neuroscience Mendelian randomization gut microbiota Alzheimer’s disease causal relationship genetic analysis |
| title | Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysis |
| title_full | Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysis |
| title_fullStr | Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysis |
| title_full_unstemmed | Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysis |
| title_short | Unraveling the connection between gut microbiota and Alzheimer’s disease: a two-sample Mendelian randomization analysis |
| title_sort | unraveling the connection between gut microbiota and alzheimer s disease a two sample mendelian randomization analysis |
| topic | Mendelian randomization gut microbiota Alzheimer’s disease causal relationship genetic analysis |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1273104/full |
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