Multi-Omics Profiling of the 42-Day Infant Gut as a Pilot Predictor of Atopic Dermatitis at One Year: A Birth Cohort Study in China

Early-life gut microbiota and metabolism are increasingly linked to immune development and atopic diseases. However, predictive microbial and metabolic markers present during the neonatal period for later atopic dermatitis (AD) remain poorly defined. This study aimed to identify early-life gut microbiome and metabolite signatures associated with the development of AD by one year of age. We conducted a prospective birth cohort study in Beijing, China, enrolling 18 infants with fecal samples collected at 42 days of age. Infants were followed for one year and classified into AD (n = 6) or non-AD (n = 12) groups. Fecal samples underwent 16S rRNA gene sequencing and untargeted metabolomic profiling. Key microbial taxa, differential metabolites, and functional pathways were identified and integrated via multi-omics correlation analysis. While overall microbial diversity was similar between groups, Staphylococcus was significantly less abundant in the AD group. Bifidobacterium and Lactobacillus showed strong correlations with lipid- and amino acid-related metabolites, including linoleic acid and N2-acetyl-L-ornithine. AD infants exhibited reduced levels of linoleic acid and choline phosphate. KEGG analysis revealed enrichment in linoleic acid metabolism, sphingolipid signaling, and AGE-RAGE signaling pathways. Integrated network analysis identified microbial-metabolite modules potentially involved in immune and barrier regulation. Multi-omics profiling of the infant gut at 42 days identified microbial and metabolic features associated with later AD development. These findings support the gut-skin axis and suggest potential early-life biomarkers for predicting AD risk and informing targeted prevention strategies.