Bioinformatics prioritisation of butyrate-associated targets and a four-gene immune-barrier score using public atopic dermatitis transcriptomic cohorts

We integrated butyrate-associated genes with the GSE32924 atopic dermatitis (AD) transcriptome and identified an exploratory four-gene transcriptomic signature (TP53, JAK2, H2AX, ALDH1A1), with sample-level AUCs of 0.951 in GSE16161, 0.888 in GSE120721 and 0.900 in GSE121212. These findings do not establish clinical transportability or disease-specific diagnostic performance. Immune analyses revealed concordant T-cell and neutrophil signals. In GSE147424, genes distributed across skin compartments but sample-level summaries did not show clear separation; donor-level mapping was unavailable. Docking and a 100-ns MD trajectory were exploratory only and did not establish HDAC3 binding. As no public cohort contained dietary, microbiome, faecal, tissue butyrate or intervention data, these hypothesis-generating findings require independent validation with donor-level, biochemical and functional studies.