Exclusive enteral nutrition in active pediatric Crohn disease: Effects on intestinal microbiota and immune regulation Tobias Schwerd, MD, Klara Frivolt,

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Presentation transcript:

Exclusive enteral nutrition in active pediatric Crohn disease: Effects on intestinal microbiota and immune regulation Tobias Schwerd, MD, Klara Frivolt, MD, Thomas Clavel, PhD, Ilias Lagkouvardos, PhD, Gabor Katona, MD, Doris Mayr, MD, Holm H. Uhlig, MD, PhD, Dirk Haller, PhD, Sibylle Koletzko, MD, Philip Bufler, MD Journal of Allergy and Clinical Immunology Volume 138, Issue 2, Pages 592-596 (August 2016) DOI: 10.1016/j.jaci.2015.12.1331 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A, Prospective study design. Disease activity was measured by mathematically weighted Pediatric Crohn's Disease Activity Index (wPCDAI), which includes assessment of abdominal pain, general well-being, stools per day, erythrocyte sedimentation rate (ESR), albumin, weight loss, perirectal disease, and extraintestinal manifestations. Clinical parameters (B) and representative endoscopic appearance (C) before dietary intervention (Pre-EEN) and after 3 weeks of EEN. D, Cytokine production of LPS-stimulated PBMCs in patients (n = 14) and noninflammatory controls (n = 5). E, Suppression of IL-6 secretion by exogenous IL-10 in LPS-stimulated PMBCs. Data are normalized to LPS-induced IL-6 release in the absence of IL-10. F, Representative fluorescence-activated cell sorting blots and quantification of Treg-cell frequency. G, Lamina propria Treg cells in paired sections (n = 12, scale bar = 50 μm). DAPI, 4′-6-diamidino-2-phenylindole, dihydrochloride. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2016 138, 592-596DOI: (10.1016/j.jaci.2015.12.1331) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A, Interprofile relationships based on generalized UniFrac distances are depicted as a nonparametric multidimensional scaling (NMDS) plot. Stool samples were collected before initiation of EEN (T1), at 2 weeks (T2), and before the end of EEN (T3) and analyzed by using high-throughput 16S rRNA gene sequencing. Individual samples are shown with corresponding patient coding letter. B, Relative sequence abundances of specific taxa and Shannon effective diversity (lower panel, right). C, Network showing significant (P < .05) and substantial correlations (strong r > |0.75|; moderate r = |0.60-0.75|) between clinical parameters and bacterial taxa. Size of taxa nodes corresponds to the average relative abundance of the given taxon (as percentage of total sequences) across all samples in which it was detected. The outer ring indicates the number of samples that were positive for the particular taxon (samples from T1 and T2). Nodes were placed to allow good visualization of highly connected nodes, independent of whether correlations were negative or positive. The length of edges has no meaning and does not reflect any parameters of the correlations. Purple: disease activity by wPCDAI; blue: PBMC stimulation with LPS or flagellin; brown: ex vivo biochemistry/fluorescence-activated cell sorting; gray: microbiota. WPCDAI, Weighted Pediatric Crohn's Disease Activity Index. Journal of Allergy and Clinical Immunology 2016 138, 592-596DOI: (10.1016/j.jaci.2015.12.1331) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Journal of Allergy and Clinical Immunology 2016 138, 592-596DOI: (10.1016/j.jaci.2015.12.1331) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Journal of Allergy and Clinical Immunology 2016 138, 592-596DOI: (10.1016/j.jaci.2015.12.1331) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions