Abstract
BACKGROUND: Asthma is a complex and heterogeneous disease presenting with a wide range of phenotypes. While prior studies have highlighted the importance of gut microbiota in asthma development, the extent of their influence varies. The exact causal links between gut microbiota and asthma remain to be fully understood, and the role of blood cell perturbation responses as potential mediators in this relationship remains unclear. METHODS: To elucidate the connections between gut microbiota, blood cell perturbation responses, and asthma, we utilized data from comprehensive genome-wide association studies (GWAS). Our investigation covered six distinct asthma phenotypes: unspecified asthma, eosinophilic asthma, allergic asthma, childhood asthma, non-allergic asthma, and obesity-related asthma. Employing Mendelian randomization (MR) techniques, we evaluated the causal associations among gut microbiota, blood cell perturbation responses, and these asthma phenotypes, primarily using inverse variance weighting (IVW) for statistical analysis. Furthermore, we examined the potential mediating effects of blood cell perturbation responses on the relationship between gut microbiota and asthma. RESULTS: Our comprehensive analysis uncovered significant interactions among gut microbiota, blood cell perturbation responses, and asthma. We pinpointed five specific blood cell perturbation responses that play a crucial role in modulating the progression of three distinct asthma phenotypes. CONCLUSION: Our investigation yields compelling evidence of causal connections between gut microbiota and asthma, with blood cell perturbation responses serving as pivotal mediators in this pathway.