Fig. 1. Associations between fecal amino acids and their derivatives with disease in pediatric patients with Crohn’s disease compared to healthy subjects.

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Fig. 1. Associations between fecal amino acids and their derivatives with disease in pediatric patients with Crohn’s disease compared to healthy subjects. Associations between fecal amino acids and their derivatives with disease in pediatric patients with Crohn’s disease compared to healthy subjects. (A) Associations with metabolic pathways as determined by Wilcoxon rank-sum test, with FDR-adjusted P < 0.05 as the cutoff. Bars indicate the number of metabolites in each category, as defined by the Human Metabolome Database (56). (B) A heat map demonstrating relative abundance of fecal amino acids and their derivatives before therapy according to the presence of disease, cluster assignment, fecal calprotectin concentration, use of antibiotics and corticosteroids, response or no response to therapy, and treatment assignment. Metadata are indicated by the color code at the top of the figure. Metabolite categories are color-coded along the left side of the heat map. White cells indicate missing data. All metabolites that were statistically different (FDR-adjusted P < 0.05) in abundance between Crohn’s disease samples and healthy controls are marked with an asterisk (*); metabolites differing significantly (FDR-adjusted P < 0.05) between cluster 1 and cluster 2 (previously defined clusters based on bacterial abundances in which cluster 1 resembled the healthy controls and cluster 2 was dysbiotic) are marked by a plus sign (+). The clusters were defined by partitioning around medoids (a centroid within a data set whose average dissimilarity to all the data points in the cluster is minimal) with estimation of number of clusters [PAMK (partitioning around medoids with estimation of number of clusters)], as previously described (5). EEN, exclusive enteral nutrition; PEN, partial enteral nutrition; FCP, fecal calprotectin; SDMA, symmetric dimethylarginine; ADMA, asymmetric dimethylarginine; GABA, γ-aminobutyric acid; NMMA, NG-methyl-l-arginine. Josephine Ni et al., Sci Transl Med 2017;9:eaah6888 Published by AAAS