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肠道微生物群与痴呆症之间的因果关系:一项孟德尔随机化研究。

Causal relationship between gut microflora and dementia: a Mendelian randomization study.

作者信息

Fu Jinjie, Qin Yuan, Xiao Lingyong, Dai Xiaoyu

机构信息

Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

出版信息

Front Microbiol. 2024 Jan 15;14:1306048. doi: 10.3389/fmicb.2023.1306048. eCollection 2023.

Abstract

BACKGROUND

Numerous pertinent investigations have demonstrated a correlation between gut microflora (GM) and the occurrence of dementia. However, a causal connection between GM and dementia and its subtypes has not yet been clarified.

OBJECTIVE

To explore the causal association between GM and dementia, including its subtypes, a two-sample Mendelian randomization (TSMR) analysis was used.

METHODS

Our data comes from the Genome-Wide Association Study (GWAS). The principal approach employed for the Mendelian randomization study was the inverse-variance weighted method, supplemented by four methods: MR-Egger, weighted median, simple mode, and weighted mode. This was followed by Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out as sensitivity analysis validation.

RESULTS

Twenty-one GMs associated with any dementia, Alzheimer's disease, vascular dementia, Lewy body dementia, Parkinson's disease, and dementia under other disease classifications were derived from the analysis, and 21 passed sensitivity tests.

CONCLUSION

We confirmed the causal relationship between GM and dementia and its subtypes, derived specific flora associated with increased or decreased risk of dementia, and provided new ideas for preventive, diagnostic, and therapeutic interventions for dementia mediated by gut microbiota.

摘要

背景

众多相关研究已证实肠道微生物群(GM)与痴呆症的发生之间存在关联。然而,GM与痴呆症及其亚型之间的因果关系尚未明确。

目的

为探讨GM与痴呆症(包括其亚型)之间的因果关联,采用了两样本孟德尔随机化(TSMR)分析。

方法

我们的数据来自全基因组关联研究(GWAS)。孟德尔随机化研究采用的主要方法是逆方差加权法,并辅以四种方法:MR-Egger法、加权中位数法、简单模式法和加权模式法。随后进行Cochrane's Q检验、MR-Egger截距检验、MR-PRESSO全局检验,并采用留一法作为敏感性分析验证。

结果

通过分析得出了21种与任何痴呆症、阿尔茨海默病、血管性痴呆、路易体痴呆、帕金森病以及其他疾病分类下的痴呆症相关的GM,其中21种通过了敏感性检验。

结论

我们证实了GM与痴呆症及其亚型之间的因果关系,得出了与痴呆症风险增加或降低相关的特定菌群,并为肠道微生物群介导的痴呆症的预防、诊断和治疗干预提供了新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf6d/10822966/6c4d50487579/fmicb-14-1306048-g001.jpg

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