Integrating the Data From Microbiome and Metabolome Genome-Wide Association Studies to Uncover Gene-Microbe-Metabolite Interactions in Allergic Diseases

Background Host genetics, gut microbiota, and metabolites have each been independently linked to allergic diseases such as asthma, allergic rhinitis, and eczema. However, the complex interactions between these three components remain poorly understood, largely due to a reliance on single-omics analyses. Integrating multi-omics data is essential for uncovering the underlying mechanisms of allergic disease pathogenesis. Methodology We performed a systematic, integrative analysis of large-scale public data from gut microbiome genome-wide association studies (GWAS) and blood metabolome-GWAS. We retrieved data from studies with cohorts of over 400 subjects. Overlapping genetic loci were identified by cross-referencing significant associations (p<1×10⁻⁶ for gene-microbe and p<1×10⁻⁵ for gene-metabolite) to define gene-microbe-metabolite trios. These trios were then cross-referenced with relevant databases (e.g., GWAS Catalog, gutMDisorder, and Human Metabolome Database (HMDB)) to establish their potential link to allergic diseases. Results Our integrative approach identified 12 distinct gene-gut microbiota-blood metabolite trios associated with allergic diseases. Established patterns were confirmed, including the ABO gene's influence on <i>Bifidobacterium bifidum</i>, which is known to impact immune regulation. Novel associations were also uncovered, including structural genes (e.g., LAMA2, PTPRT) potentially facilitating microbiota attachment and modulating metabolites such as octadecanedioate and genes involved in neurotransmitter signaling (e.g., SYN3, PDE1A), suggesting potential neuro-immune mechanisms. Conclusions By integrating microbiome-GWAS and metabolome-GWAS data, we have generated a valuable resource of candidate pathways underlying allergic disease pathogenesis. The identified trios provide specific, testable hypotheses for future validation studies and potential targets for biomarker discovery. This work underscores the power of multi-omics integration in allergy research and provides a clear roadmap for investigating complex gene-environment interactions.