Causal associations among gut microbiota, 1400 plasma metabolites, and asthma: a two-sample Mendelian randomization study

Background: Emerging evidence indicates a correlation between imbalances in intestinal microbiota and changes in plasma metabolites in the progression of asthma. However, the causal link between these factors remains unclear. Methods: A two-sample Mendelian randomization (MR) study was employed to evaluate the potential causal connection between gut microbiota, plasma metabolites, and asthma susceptibility. Gut microbiota data from expansive genome-wide genotype studies and 16S fecal microbiome datasets were examined by the MiBioGen Alliance. Asthma data were procured from the FinnGen biobank analysis, while comprehensive Genome-Wide Association Studies (GWAS) summary statistics for plasma metabolites were derived from the NHGRI-EBI GWAS Catalog. Fluctuations in intestinal flora and plasma metabolites in asthma patients were evaluated using the weighted mode method. Additionally, pleiotropic and heterogeneity analyses were performed to ascertain the reliability of the findings. Results: Upon examining the gut microbiota through MR with the IVW method, alongside tests for heterogeneity and pleiotropy, findings reveal a negative association between the abundance of the Christensenellaceae R.7 group and asthma risk. In contrast, the Bifidobacterium and Prevotella 7 genera exhibit a positive association with asthma risk, indicating they may be potential risk factors (p < 0.05). Furthermore, MR analysis of 1,400 metabolites employing Weighted median, IVW, and Weighted mode methods resulted in p-values below 0.05. Subsequent tests for pleiotropy and heterogeneity showed that the levels of 3,5-dichloro-2,6-dihydroxybenzoic acid have a negative correlation with asthma, whereas the phenylalanine to phosphate ratio has a positive correlation, suggesting their potential as risk factors for asthma (p < 0.05). Conclusion: The current Mendelian randomization study provides evidence supporting a potential causal link between specific gut microbiota taxa, plasma metabolites, and asthma. These findings offer novel perspectives for future research and the development of treatment and prevention strategies for asthma.