Assessing causal relationships between gut microbiota and asthma: evidence from two sample Mendelian randomization analysis

Rong Li; Qi Guo; Jian Zhao; Wenhui Kang; Ruoyu Lu; Zichong Long; Lili Huang; Yiting Chen; Anda Zhao; Jinhong Wu; Yong Yin; Shenghui Li

doi:10.3389/fimmu.2023.1148684

Assessing causal relationships between gut microbiota and asthma: evidence from two sample Mendelian randomization analysis

Front Immunol. 2023 Jul 19:14:1148684. doi: 10.3389/fimmu.2023.1148684. eCollection 2023.

Authors

Rong Li¹, Qi Guo², Jian Zhao¹, Wenhui Kang¹, Ruoyu Lu¹, Zichong Long¹, Lili Huang¹, Yiting Chen¹, Anda Zhao³, Jinhong Wu⁴, Yong Yin⁴, Shenghui Li¹

Affiliations

¹ Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² School Health Department, Shanghai Center for Disease Control and Prevention, Shanghai, China.
³ Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background: 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.

Methods: 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.

Results: In the absence of heterogeneity and horizontal pleiotropy, the IVW method revealed that genetically predicted Barnesiella and RuminococcaceaeUCG014 were positively correlated with the risk of asthma, while the association between genetically predicted CandidatusSoleaferrea and asthma was negative. And for the three phenotypes of asthma, genetically predicted Akkermansia reduced the risk of adult-onset asthma, Collinsella and RuminococcaceaeUCG014 increased the risk of childhood-onset asthma, and FamilyXIIIAD3011group, Eisenbergiella, and Ruminiclostridium6 were correlated with the risk of moderate-severe asthma (all P<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.

Conclusion: 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.

Keywords: Mendelian randomization; asthma; causality; childhood-onset asthma; gut microbiota.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Asthma* / genetics
Dysbiosis
Gastrointestinal Microbiome*
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis

Grants and funding

This was not an industry-supported study. The study was funded by grants from the National Natural Science Foundation of China (82273651, 81874266, 81673183), special grant for Preschool Children’s Health Management from the Shanghai Municipal Education Commission, Key Project from Shanghai Municipal Science and Technology Commission (18411951600), Major Science and Technology Projects of Hainan Province (ZDKJ2019010), and Key Science and Technology Cooperation Projects of Hainan Province (ZDYF2020210).