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.