Multiomics-empowered Deep Phenotyping of Ulcerative Colitis Identifies Biomarker Signatures Reporting Functional Remission States.

Autor: Janker L; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., Schuster D; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., Bortel P; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., Hagn G; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., Meier-Menches SM; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.; Joint Metabolome Facility, University of Vienna, Vienna, Austria., Mohr T; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.; Joint Metabolome Facility, University of Vienna, Vienna, Austria., Mader JC; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., Slany A; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., Bileck A; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.; Joint Metabolome Facility, University of Vienna, Vienna, Austria., Brunmair J; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., Madl C; Institute of Pathology and Microbiology, Krankenanstalt Rudolfstiftung, Vienna, Austria., Unger L; Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria., Hennlich B; Institute of Pathology and Microbiology, Krankenanstalt Rudolfstiftung, Vienna, Austria., Weitmayr B; Institute of Pathology and Microbiology, Krankenanstalt Rudolfstiftung, Vienna, Austria., Del Favero G; Core Facility Multimodal Imaging, Faculty of Chemistry, University of Vienna, Vienna, Austria., Pils D; Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria., Pukrop T; Department of Internal Medicine III, Hematology and Oncology, University Hospital Regensburg, Regensburg, Germany., Pfisterer N; Institute of Pathology and Microbiology, Krankenanstalt Rudolfstiftung, Vienna, Austria., Feichtenschlager T; Institute of Pathology and Microbiology, Krankenanstalt Rudolfstiftung, Vienna, Austria., Gerner C; Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.; Joint Metabolome Facility, University of Vienna, Vienna, Austria.
Jazyk: angličtina
Zdroj: Journal of Crohn's & colitis [J Crohns Colitis] 2023 Oct 20; Vol. 17 (9), pp. 1514-1527.
DOI: 10.1093/ecco-jcc/jjad052
Abstrakt: Introduction: Ulcerative colitis [UC] is a chronic disease with rising incidence and unclear aetiology. Deep molecular phenotyping by multiomics analyses may provide novel insights into disease processes and characteristic features of remission states.
Methods: UC pathomechanisms were assessed by proteome profiling of human tissue specimens, obtained from five distinct colon locations for each of the 12 patients included in the study. Systemic disease-associated alterations were evaluated thanks to a cross-sectional setting of mass spectrometry-based multiomics analyses comprising proteins, metabolites, and eicosanoids of plasma obtained from UC patients during acute episodes and upon remission, in comparison with healthy controls.
Results: Tissue proteome profiling indicated colitis-associated activation of neutrophils, macrophages, B and T cells, fibroblasts, endothelial cells and platelets, and hypoxic stress, and suggested a general downregulation of mitochondrial proteins accompanying the establishment of apparent wound healing-promoting activities including scar formation. Whereas pro-inflammatory proteins were apparently upregulated by immune cells, the colitis-associated epithelial cells, fibroblasts, endothelial cells, and platelets seemed to predominantly contribute anti-inflammatory and wound healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulations of gut and gut microbiome-derived metabolites. Upon remission several, but not all, molecular candidate biomarker levels recovered back to normal.
Conclusion: The findings may indicate that microvascular damage and platelet deregulation hardly resolve upon remission, but apparently persist as disease-associated molecular signatures. This study presents local and systemic molecular alterations integrated in a model for UC pathomechanisms, potentially supporting the assessment of disease and remission states in UC patients.
(© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)
Databáze: MEDLINE
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