Dysbiosis Involving Methionine and PPAR-γ Pathways is Associated with Early Onset Atopic Dermatitis and Food Allergy.

BACKGROUND:Atopic dermatitis (AD) and food allergy (FA) often originate early in life. Gut microbiota interactions with the host immune system influence allergy development, yet the distinct gut microbiome and functional profiles in individuals with AD, FA, or both AD+FA remain underexplored. OBJECTIVE:We investigated microbial colonization and proteomic profiles in infants with AD, FA, and AD+FA compared to age- and sex-matched controls from the Allergy Development in Early Life and Associated Factors in the Thai Birth Cohort (ALICE). METHODS:Gut microbiomes from stool samples were analyzed using 16S sequencing, and proteomic analysis was conducted by liquid chromatography-tandem mass spectrometry. RESULTS:The study included 16 AD, 5 FA, 5 AD+FA subjects, and 26 controls. AD+FA group exhibited the most severe dysbiosis. Enrichment of proteins involved in methionine biosynthesis in Bifidobacterium scardovii and high Erysipelotrichaceae colonization suggest a link to high-fat diets, known to reduce intestinal short-chain fatty acid and serotonin levels, contributing to allergies. Erysipelotrichaceae in AD+FA groups also expressed proteins related to histidine degradation. Low Bifidobacteriaceae levels were noted in FA and AD+FA, with more pathogenic strains colonized. Increased Bacteroidaceae in FA and AD+FA and Enterobacteriaceae in FA were detected. Pathways involving vitamin B1, a ligand for proliferator-activated receptor-γ (PPAR-γ) from Enterobacteriaceae could promote TH2 cells, type 2 innate lymphoid cells, and M2 macrophages, likely contribute to allergic inflammation. CONCLUSIONS:AD+FA phenotype exhibited the most distinctive gut microbiome alterations, highlighting unique dysbiosis patterns. Microbiome biosynthesis pathways involving metabolism of methionine, histidine, serotonin, and vitamin B1 point to new targets for modifying or treating AD and FA.