Background:Asthma is a multifactorial condition where patients with identical clinical diagnoses do not have the same clinical history or respond to treatment. This clinical heterogeneity is reflected in the definition of two main endotypes. We aimed to explore the metabolic and microbiota signatures that characterize the clinical allergic asthma phenotype in obese children.Methods:We used a multi-omics approach combining clinical data, plasma and fecal inflammatory biomarkers, metagenomics, and metabolomics data in a cohort of allergic asthmatic children.Results:We observed that the obese allergic asthmatic phenotype was markedly associated with higher levels of leptin and lower relative proportions of plasma acetate and a member from theClostridialesorder. Moreover, allergic children with a worse asthma outcome showed higher levels of large unstained cells, fecal D lactate and D/L lactate ratio, and with a higher relative proportion of plasma creatinine and an unclassified family member from the RF39 order belonging to the Mollicutes class. Otherwise, children with persistent asthma presented lower levels of plasma citrate and dimethylsulfone.Conclusion:Our integrative approach shows the molecular heterogeneity of the allergic asthma phenotype while highlighting the use of omics technologies to examine the clinical phenotype at a more holistic level.