Integrated Multi-omics Reveals Different Host Crosstalk of Atopic Dermatitis-Enriched Bifidobacterium longum Strains

The infant gut microbiome is critical for future human health and is associated with atopic dermatitis (AD); however, numerous underlying mechanisms remain unexplored. Our study investigated gut microbiome-host relationships in infants with AD and healthy controls, focusing on the Bifidobacterium longum subclades through multi-omics. We conducted a metagenomic analysis of the gut microbiome in 31 AD patients and 29 healthy controls at six months to profile the microbiome community, including strain-level phylogenetic and pan-genomic analyses. Subsequently, colonocyte transcriptomics and untargeted metabolomics were employed to integrate the associations among each omics. Our results unveiled distinct B. longum subclades in both groups, harboring unique genes related to ecological colonization. These subclades influenced the stability of gut microbial diversity, suggesting an indirect role of B. longum in influencing AD through microbial diversity modulation ( P  < 0.05). Depending on the B. longum subclade, the host transcriptome ignificantly correlated with phosphatidylinositol 3-kinase-AKT signaling, neuroactive ligand-receptor interactions, and cell signaling pathways. Metabolomic analysis revealed distinct metabolite associations for each subclade, including tetrahydrocortisol, N-palmitoyl GABA, and ornithine—all related to stress and neuromodulation. These findings indicate contrasting effects on the gut immune and nervous systems by different B. longum subclades in AD and healthy infants. B. longum subclades displayed varied associations with the host's transcriptome and metabolite profiles, suggesting they may play a pivotal role in stabilizing the enteric immune and nervous systems, potentially influencing AD development. Our findings emphasize the importance of strain-level variations in microbiome studies and provide novel perspectives on host interactions related to AD.