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肠道菌群与过敏性疾病的因果关系:来自双向两样本孟德尔随机化分析的见解。

The causality between intestinal flora and allergic diseases: Insights from a bi-directional two-sample Mendelian randomization analysis.

机构信息

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Graduate School, Beijing University of Chinese Medicine, Beijing, China.

出版信息

Front Immunol. 2023 Mar 9;14:1121273. doi: 10.3389/fimmu.2023.1121273. eCollection 2023.

Abstract

BACKGROUND

Growing evidence shows a significant association between intestinal flora and allergic diseases, specifically atopic dermatitis (AD), allergic rhinitis (AR), and allergic asthma (AA). However, the causality has not yet been clarified.

OBJECTIVE

We conducted a bidirectional two-sample Mendelian randomization (TSMR) analysis to study the causal relationships between intestinal flora classification and AD, AR, or AA.

MATERIALS AND METHODS

We obtained summary data of intestinal flora, AD, AR, and AA from a genome-wide association research. The inverse-variance weighted method is the primary method for analyzing causality in the TSMR analysis. Several sensitivity analyses were conducted to examine the stability of TSMR results. Reverse TSMR analysis was also performed to assess whether there was a reverse causality.

RESULTS

A total of 7 bacterial taxa associated with AD, AR, and AA were identified by the current TSMR analysis. Specifically, the genus Dialister(=0.034)and genus Prevotella(=0.047)were associated with a higher risk of AD, whereas class Coriobacteriia (=0.034) and its child taxon, order Coriobacteriales (=0.034) and family Coriobacteriaceae (=0.034), all had a protective effect on AR. In addition, the family Victivallaceae (=0.019) was identified as a risk factor for AR. We also noticed a positive association between the genus Holdemanella (=0.046) and AA. The reverse TSMR analysis didn't suggest any evidence of reverse causality from allergic diseases to the intestinal flora.

CONCLUSION

We confirmed the causal relationship between intestinal flora and allergic diseases and provided an innovative perspective for research on allergic diseases: targeted regulation of dysregulation of specific bacterial taxa to prevent and treat AD, AR, and AA.

摘要

背景

越来越多的证据表明,肠道菌群与过敏疾病之间存在显著关联,特别是特应性皮炎(AD)、过敏性鼻炎(AR)和过敏性哮喘(AA)。然而,因果关系尚未阐明。

目的

我们进行了双向两样本孟德尔随机化(TSMR)分析,以研究肠道菌群分类与 AD、AR 或 AA 之间的因果关系。

材料和方法

我们从全基因组关联研究中获得了肠道菌群、AD、AR 和 AA 的汇总数据。逆方差加权法是 TSMR 分析中分析因果关系的主要方法。我们进行了几种敏感性分析,以检查 TSMR 结果的稳定性。还进行了反向 TSMR 分析,以评估是否存在反向因果关系。

结果

通过当前的 TSMR 分析,确定了 7 种与 AD、AR 和 AA 相关的细菌分类群。具体来说,属 Dialister(=0.034)和属 Prevotella(=0.047)与 AD 风险增加相关,而类 Coriobacteriia(=0.034)及其子分类群,目 Coriobacteriales(=0.034)和科 Coriobacteriaceae(=0.034),均对 AR 具有保护作用。此外,科 Victivallaceae(=0.019)被确定为 AR 的危险因素。我们还注意到属 Holdemanella(=0.046)与 AA 之间存在正相关。反向 TSMR 分析并未提示过敏疾病对肠道菌群存在任何反向因果关系的证据。

结论

我们证实了肠道菌群与过敏疾病之间的因果关系,并为过敏疾病的研究提供了一个创新视角:靶向调节特定细菌分类群的失调,以预防和治疗 AD、AR 和 AA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e9b/10033526/186b669bffd5/fimmu-14-1121273-g001.jpg

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