Causal relationship between gut microbiome and childhood allergy: A bidirectional Mendelian randomization analysis

This study aims to investigate the potential causal relationship between gut microbiome pathways and childhood allergy risk using a bidirectional Mendelian randomization (MR) approach. We conducted a bidirectional MR analysis using inverse variance weighting methods to assess the suggestive causal relationship between gut microbiome pathways and childhood allergy. The reverse MR analysis revealed that childhood allergy showed suggestive causal associations with several microbial features. For metabolic pathways, a higher risk of childhood allergy was associated with Lipid IV~A~ biosynthesis (odds ratio [OR] 1.11, 95% confidence interval [CI]: 1.00-1.22, P = .044) and NAD salvage pathway I (OR 1.14, 95% CI: 1.01-1.28, P = .030). At the taxonomic level, a lower risk of childhood allergy was associated with Bacteroidaceae (OR 0.90, 95% CI: 0.81-0.99, P = .031), Adlercreutzia (OR 0.79, 95% CI: 0.67-0.92, P = .003), Bacteroidales (OR 0.90, 95% CI: 0.81-0.99, P = .031), Roseburia (OR 0.89, 95% CI: 0.80-0.99,P = .032), Adlercreutzia equolifaciens (OR 0.79, 95% CI: 0.67-0.92, P = .003),Holdemania (unclassified) (OR 0.79, 95% CI: 0.64-0.98, P = .028), and Bacteroides vulgatus (OR 0.86, 95% CI: 0.78-0.95, P = .004). This study provides evidence for the potential causal relationship between specific gut microbiome pathways and childhood allergy. Several gut microbial features demonstrated suggestive causal associations with childhood allergy risk. For metabolic pathways, inverse associations (suggesting protective effects) were observed for creatinine.degradation I (OR 0.86, 95% CI: 0.76-0.98, P = .021) and superpathway of pyrimidine ribonucleosides degradation (OR 0.75, 95% CI: 0.62-0.91, P = .004). Conversely, positive associations with allergy risk were identified for isoleucine biosynthesis I from.threonine(OR 1.22, 95% CI: 1.00-1.48, P = .049), glutamate degradation V via hydroxyglutarate (OR 1.15, 95% CI: 1.01-1.32, P = .040), superpathway of polyamine biosynthesis II (OR 1.15, 95% CI: 1.01-1.32, P = .035), allantoin degradation to glyoxylate III (OR 1.17, 95% CI: 1.02-1.33, P = .024), and UDP N acetyl D glucosamine biosynthesis I (OR 1.50, 95% CI: 1.11-2.02, P = .008). At the taxonomic level, inverse associations were found for Odoribacter splanchnicus (OR 0.73, 95% CI: 0.58-0.91, P = .005) and Coprococcussp.ART55/1 (OR 0.84, 95% CI: 0.73-0.97, P = .014). Positive associations with allergy risk were observed for Betaproteobacteria (OR 1.29, 95% CI: 1.06-1.58, P = .013), Lactobacillaceae (OR 1.16, 95% CI: 1.04-1.30, P = .010), Clostridiaceae (OR 1.14, 95% CI: 1.01-1.29, P = .033), Clostridium (OR 1.15, 95% CI: 1.00-1.31, P = .046), Burkholderiales (OR 1.29, 95% CI: 1.06-1.58, P = .013), and Eubacterium hallii (OR 1.24, 95% CI: 1.08-1.41, P = .002).This study provides evidence for the potential causal relationship between specific gut microbiome pathways and childhood allergy.