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Mucosal and Plasma Metabolomes in New-onset Paediatric Inflammatory Bowel Disease: Correlations with Disease Characteristics and Plasma Inflammation Protein Markers.
Nyström, Niklas; Prast-Nielsen, Stefanie; Correia, Mario; Globisch, Daniel; Engstrand, Lars; Schuppe-Koistinen, Ina; Halfvarson, Jonas.
Afiliación
  • Nyström N; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
  • Prast-Nielsen S; Centre for Translational Microbiome Research, Karolinska Institutet, Stockholm, Sweden.
  • Correia M; Department of Chemistry - BMC, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Globisch D; Centre for Translational Microbiome Research, Karolinska Institutet, Stockholm, Sweden.
  • Engstrand L; Department of Chemistry - BMC, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Schuppe-Koistinen I; Centre for Translational Microbiome Research, Karolinska Institutet, Stockholm, Sweden.
  • Halfvarson J; Centre for Translational Microbiome Research, Karolinska Institutet, Stockholm, Sweden.
J Crohns Colitis ; 17(3): 418-432, 2023 Apr 03.
Article en En | MEDLINE | ID: mdl-36219554
ABSTRACT
BACKGROUND AND

AIMS:

To advance the understanding of inflammatory bowel disease [IBD] pathophysiology, we compared the mucosal and plasma metabolomes between new-onset paediatric IBD patients and symptomatic non-IBD controls, and correlated plasma inflammation markers and disease characteristics with the altered metabolites.

METHODS:

Paired colonic and ileal biopsies and plasma from 67 treatment-naïve children with incident Crohn's disease [CD; n = 47], ulcerative colitis [UC; n = 9], and non-IBD controls [n = 11] were analysed using ultra-performance liquid chromatography-mass spectrometry [UPLC-MS/MS]. Inflammatory plasma proteins [n = 92] were assessed.

RESULTS:

The metabolomes in inflamed mucosal biopsies differed between IBD patients and controls. In CD, mucosal levels of several lysophospholipids [lysophosphatidylcholines, lysophosphatidyletanolamines, lysophosphatidylinositols, and lysophosphatidylserines] were decreased, correlating with various plasma metabolites including amino acid analogues and N-acetylated compounds. In both CD and UC, mucosal sphingolipids, including ceramide [d182/241, d181/242], lactosyl-N-palmitoyl-sphingosine [d181/160], behenoyl sphingomyelin [d181/220], lignoceroyl sphingomyelin [d181/240], and/or sphingomyelin [d181/241, d182/240] were increased, correlating with sphingolipids, bile acids, and/or N-acetylated metabolites in plasma. Among proteins associated with CD, interleukin-24 correlated with plasma metabolites, including lactosyl-N-palmitoyl sphingosine [d181/160] and phosphatidyletanolamine [181/181], haemoglobin, and faecal calprotectin. In UC, interleukin-24, interleukin-17A, and C-C motif chemokine 11 correlated with several plasma metabolites, including N-acetyltryptophan, tryptophan, glycerate, and threonate, and with the Paediatric Ulcerative Colitis Activity Index, C-reactive protein, and faecal calprotectin.

CONCLUSIONS:

Mucosal perturbations of lysophospholipids and sphingolipids characterised the metabolome in new-onset paediatric IBD and correlated with plasma metabolites. By integrating plasma metabolomics data with inflammatory proteins and clinical data, we identified clinical and inflammatory markers associated with metabolomic signatures for IBD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Colitis Ulcerosa Tipo de estudio: Prognostic_studies Límite: Child / Humans Idioma: En Revista: J Crohns Colitis Asunto de la revista: GASTROENTEROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Suecia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Colitis Ulcerosa Tipo de estudio: Prognostic_studies Límite: Child / Humans Idioma: En Revista: J Crohns Colitis Asunto de la revista: GASTROENTEROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Suecia