Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
School Health Department, Shanghai Center for Disease Control and Prevention, Shanghai, China.
Front Immunol. 2023 Jul 19;14:1148684. doi: 10.3389/fimmu.2023.1148684. eCollection 2023.
Accumulating evidence has suggested that gut microbiota dysbiosis is commonly observed in asthmatics. However, it remains unclear whether dysbiosis is a cause or consequence of asthma. We aimed to examine the genetic causal relationships of gut microbiota with asthma and its three phenotypes, including adult-onset asthma, childhood-onset asthma, and moderate-severe asthma.
To elucidate the causality of gut microbiota with asthma, we applied two sample Mendelian randomization (MR) based on the largest publicly available genome-wide association study (GWAS) summary statistics. Inverse variance weighting meta-analysis (IVW) was used to obtain the main estimates; and Weighted median, MR-Egger, Robust Adjusted Profile Score (MR-RAPS), Maximum likelihood method (ML), and MR pleiotropy residual sum and outlier (MR-PRESSO) methods were applied in sensitivity analyses. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation.
In the absence of heterogeneity and horizontal pleiotropy, the IVW method revealed that genetically predicted and were positively correlated with the risk of asthma, while the association between genetically predicted and asthma was negative. And for the three phenotypes of asthma, genetically predicted reduced the risk of adult-onset asthma, and increased the risk of childhood-onset asthma, and , , and were correlated with the risk of moderate-severe asthma (all <0.05). The reverse MR analysis didn't find evidence supporting the reverse causality from asthma and its three phenotypes to the gut microbiota genus.
This study suggested that microbial genera were causally associated with asthma as well as its three phenotypes. The findings deepened our understanding of the role of gut microbiota in the pathology of asthma, which emphasizes the potential of opening up a new vista for the prevention and diagnosis of asthma.
越来越多的证据表明，肠道微生物群落失调在哮喘患者中普遍存在。然而，肠道微生物群落失调是哮喘的原因还是结果仍不清楚。我们旨在研究肠道微生物群落与哮喘及其三种表型（成人起病哮喘、儿童起病哮喘和中重度哮喘）之间的遗传因果关系。
为了阐明肠道微生物群落与哮喘之间的因果关系，我们应用了基于最大公开可用全基因组关联研究（GWAS）汇总统计数据的两种样本 Mendelian 随机化（MR）方法。逆方差加权荟萃分析（IVW）用于获得主要估计值；加权中位数、MR-Egger、稳健调整轮廓评分（MR-RAPS）、最大似然法（ML）和 MR 偏倚残差和异常值（MR-PRESSO）方法用于敏感性分析。最后，进行了反向 MR 分析以评估反向因果关系的可能性。
在不存在异质性和水平偏倚的情况下，IVW 方法表明，遗传预测的 和 与哮喘风险呈正相关，而遗传预测的 与哮喘之间的关联呈负相关。对于哮喘的三种表型，遗传预测的 降低了成人起病哮喘的风险， 和 增加了儿童起病哮喘的风险， 和 、 、 和 与中重度哮喘的风险相关（均<0.05）。反向 MR 分析没有发现证据支持哮喘及其三种表型从因果关系到肠道微生物群落属的反方向。
本研究表明，微生物属与哮喘及其三种表型存在因果关系。这些发现加深了我们对肠道微生物在哮喘发病机制中的作用的理解，强调了为哮喘的预防和诊断开辟新视野的潜力。
