@article{crestani_harb_charbonnier_leirer_motsinger-reif_rachid_phipatanakul_kaddurah-daouk_chatila_2020, title={Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma}, volume={145}, ISSN={["1097-6825"]}, DOI={10.1016/j.jaci.2019.10.014}, abstractNote={BackgroundFood allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed.ObjectiveWe sought to apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in patients with FA.MethodsMass spectrometry–based untargeted metabolomic profiling was performed on serum samples of children with either FA alone, asthma alone, or both FA and asthma, as well as healthy pediatric control subjects.ResultsIn this pilot study patients with FA exhibited a disease-specific metabolomic signature compared with both control subjects and asthmatic patients. In particular, FA was uniquely associated with a marked decrease in sphingolipid levels, as well as levels of a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T cells. Specific comparison of patients with FA and asthmatic patients revealed differences in the microbiota-sensitive aromatic amino acid and secondary bile acid metabolism. Children with both FA and asthma exhibited a metabolomic profile that aligned with that of FA alone but not asthma. Among children with FA, the history of severe systemic reactions and the presence of multiple FAs were associated with changes in levels of tryptophan metabolites, eicosanoids, plasmalogens, and fatty acids.ConclusionsChildren with FA have a disease-specific metabolomic profile that is informative of disease mechanisms and severity and that dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in children with FA might reflect the interplay between an altered microbiota and immune cell subsets in the gut. Food allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed. We sought to apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in patients with FA. Mass spectrometry–based untargeted metabolomic profiling was performed on serum samples of children with either FA alone, asthma alone, or both FA and asthma, as well as healthy pediatric control subjects. In this pilot study patients with FA exhibited a disease-specific metabolomic signature compared with both control subjects and asthmatic patients. In particular, FA was uniquely associated with a marked decrease in sphingolipid levels, as well as levels of a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T cells. Specific comparison of patients with FA and asthmatic patients revealed differences in the microbiota-sensitive aromatic amino acid and secondary bile acid metabolism. Children with both FA and asthma exhibited a metabolomic profile that aligned with that of FA alone but not asthma. Among children with FA, the history of severe systemic reactions and the presence of multiple FAs were associated with changes in levels of tryptophan metabolites, eicosanoids, plasmalogens, and fatty acids. Children with FA have a disease-specific metabolomic profile that is informative of disease mechanisms and severity and that dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in children with FA might reflect the interplay between an altered microbiota and immune cell subsets in the gut.}, number={3}, journal={JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}, author={Crestani, Elena and Harb, Hani and Charbonnier, Louis-Marie and Leirer, Jonathan and Motsinger-Reif, Alison and Rachid, Rima and Phipatanakul, Wanda and Kaddurah-Daouk, Rima and Chatila, Talal A.}, year={2020}, month={Mar}, pages={897–906} }
 @article{crestani_leirer_motsinger-reif_phipatanakul_kaddurah-daouk_chatila_2019, title={Untargeted Metabolomic Profiling Identifies Disease-Specific Pathways in Food Allergy and Asthma}, volume={143}, ISSN={["1097-6825"]}, DOI={10.1016/j.jaci.2018.12.778}, abstractNote={Food allergy (FA) affects an increasing proportion of children in the US and other developed countries for reasons that remain largely unknown. A deeper understanding of pathogenic mechanisms active in FA may lead to much needed diagnostic and prognostic biomarkers of disease and improved treatment options. Children with asthma alone, children with FA alone, children with both FA and asthma as well as healthy pediatric controls were recruited in the Allergy clinic at Boston Children’s Hospital. Mass spectrometry-based untargeted metabolomic profiling was performed on serum samples (n=35 for FA or asthma alone and FA/asthma; n=20 for controls) looking at global metabolism. Untargeted metabolomic analysis revealed differential profiles of altered metabolites in patients’ groups. In comparison to both controls and children with asthma, FA was uniquely associated with a marked decrease in sphingolipids - in particular sphingomyelins and ceramides - as well as lysophospholipids. Among atopic children, differences in aromatic amino acid metabolism and metabolism of secondary bile acids were observed between food allergic and asthmatic children. Among children with FA, the metabolomic profile of those with asthma was indistinguishable from that of children without asthma. Both unique and shared metabolomic alterations were detected in children with FA, asthma, or both, likely reflecting overlapping but distinct mechanisms and environmental influences operative in these disorders. Lower levels of sphingolipids and ceramides observed in food allergic children may affect the interplay between microbiota and immune cell subsets in the gut, including iNKT cells.}, number={2}, journal={JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}, author={Crestani, Elena and Leirer, Jonathan and Motsinger-Reif, Alison and Phipatanakul, Wanda and Kaddurah-Daouk, Rima and Chatila, Talal A.}, year={2019}, month={Feb}, pages={AB255–AB255} }