Multi-omics empowered deep phenotyping of ulcerative colitis identifies biomarker signatures reporting functional remission states
- Author(s)
- Lukas Janker, Dina Schuster, Patricia Bortel, Gerhard Hagn, Samuel M Meier-Menches, Thomas Mohr, Johanna C Mader, Astrid Slany, Andrea Bileck, Julia Brunmair, Christian Madl, Lukas Unger, Barbara Hennlich, Barbara Weitmayr, Giorgia Del Favero, Dietmar Pils, Tobias Pukrop, Nikolaus Pfisterer, Thomas Feichtenschlager, Christopher Gerner
- Abstract
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.
- Organisation(s)
- Department of Analytical Chemistry, Joint Metabolome Facility, Department of Inorganic Chemistry, Core Facility Multimodal Imaging, Department of Food Chemistry and Toxicology, Mass Spectrometry Centre
- External organisation(s)
- Medizinische Universität Wien, Krankenanstalt Rudolfstiftung, University Hospital Regensburg
- Journal
- Journal of Crohn's & colitis
- Volume
- 17
- Pages
- 1514-1527
- No. of pages
- 14
- ISSN
- 1873-9946
- DOI
- https://doi.org/10.1093/ecco-jcc/jjad052
- Publication date
- 09-2023
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 302016 Gastroenterology, 106037 Proteomics, 301303 Medical biochemistry
- Keywords
- ASJC Scopus subject areas
- General Medicine
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/64cfa9b2-eed8-46cf-bd1e-0ddeeb271b63