Genetically predicted gut microbiota and risk of pediatric asthma and food allergy in East Asian populations: a two-sample Mendelian randomization study

OBJECTIVE: To investigate the genetically predicted associations between gut microbiota composition and the risk of pediatric asthma and food allergy in East Asian populations using a bidirectional two-sample Mendelian randomization (MR) approach. METHODS: We performed bidirectional two-sample MR analyses using summary-level genome-wide association study (GWAS) data. Genetic instruments for 500 gut microbial taxa were obtained from the 4D-SZ cohort, which included 3,432 Chinese individuals who underwent whole-metagenome shotgun sequencing. Outcome GWAS summary statistics for pediatric asthma (547 cases and 161,803 controls; GCST90018675) and food allergy (3,777 cases and 165,939 controls; GCST90018625) were derived from the Biobank Japan project. All participants were of East Asian ancestry. The primary MR analysis was conducted using the inverse-variance weighted (IVW) method, with MR-Egger, weighted median, and weighted mode analyses used as complementary approaches. Sensitivity analyses included Cochran's Q test for heterogeneity, the MR-Egger intercept test for horizontal pleiotropy, and MR-PRESSO for outlier detection. RESULTS: The IVW analysis identified nine gut microbial taxa with nominally significant associations with pediatric asthma risk (p < 0.05). Among them, Subdoligranulum showed a suggestive protective association (OR = 0.91, 95% CI: 0.83-0.99), whereas Solobacterium showed a suggestive risk association (OR = 1.08, 95% CI: 1.00-1.16). For food allergy, eighteen taxa were nominally associated with disease risk (p < 0.05). Bacteroides helcogenes showed a suggestive protective association (OR = 0.96, 95% CI: 0.94-0.98), whereas Alistipes shahii showed a suggestive risk association (OR = 1.03, 95% CI: 1.00-1.05). Sensitivity analyses yielded generally consistent results. Reverse MR analyses did not identify significant genetically predicted effects of pediatric asthma or food allergy on gut microbiota composition. CONCLUSION: This exploratory MR study provides suggestive evidence that specific gut microbial taxa may be associated with pediatric asthma and food allergy in East Asian populations. These findings offer preliminary support for the role of the gut microbiota in allergic diseases and underscore the importance of population-specific research. Further large-scale studies with stricter multiple-testing correction are needed to validate these associations.