Unique Metabolomic and Lipidomic Profile in Serum From Patients With Crohn's Disease and Ulcerative Colitis Compared With Healthy Control Individuals

Hauke Christian Tews; Franziska Schmelter; Arne Kandulski; Christa Büchler; Stephan Schmid; Sophie Schlosser; Tanja Elger; Johanna Loibl; Stefanie Sommersberger; Tanja Fererberger; Stefan Gunawan; Claudia Kunst; Karsten Gülow; Dominik Bettenworth; Bandik Föh; Carlos Maaß; Philipp Solbach; Ulrich L Günther; Stefanie Derer; Jens U Marquardt; Christian Sina; Martina Müller

doi:10.1093/ibd/izad298

Unique Metabolomic and Lipidomic Profile in Serum From Patients With Crohn's Disease and Ulcerative Colitis Compared With Healthy Control Individuals

Inflamm Bowel Dis. 2023 Dec 29:izad298. doi: 10.1093/ibd/izad298. Online ahead of print.

Authors

Hauke Christian Tews¹, Franziska Schmelter², Arne Kandulski¹, Christa Büchler¹, Stephan Schmid¹, Sophie Schlosser¹, Tanja Elger¹, Johanna Loibl¹, Stefanie Sommersberger¹, Tanja Fererberger¹, Stefan Gunawan¹, Claudia Kunst¹, Karsten Gülow¹, Dominik Bettenworth^{3

4}, Bandik Föh⁵, Carlos Maaß⁵, Philipp Solbach⁵, Ulrich L Günther⁶, Stefanie Derer², Jens U Marquardt⁵, Christian Sina^{2

5

7}, Martina Müller¹

Affiliations

¹ Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.
² Institute of Nutritional Medicine, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
³ Department of Medicine B-Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany.
⁴ Practice for Internal Medicine, Münster, Germany.
⁵ Department of Medicine I, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
⁶ Institute of Chemistry and Metabolomics, University of Lübeck, Lübeck, Germany.
⁷ Fraunhofer Research Institution for Individualized and Cell-Based Medical Engineering, Lübeck, Germany.

PMID: 38156773
DOI: 10.1093/ibd/izad298

Abstract

Background: Accurate biomarkers for disease activity and progression in patients with inflammatory bowel disease (IBD) are a prerequisite for individual disease characterization and personalized therapy. We show that metabolic profiling of serum from IBD patients is a promising approach to establish biomarkers. The aim of this work was to characterize metabolomic and lipidomic serum profiles of IBD patients in order to identify metabolic fingerprints unique to the disease.

Methods: Serum samples were obtained from 55 patients with Crohn's disease (CD), 34 patients with ulcerative colitis (UC), and 40 healthy control (HC) individuals and analyzed using proton nuclear magnetic resonance spectroscopy. Classification of patients and HC individuals was achieved by orthogonal partial least squares discriminant analysis and univariate analysis approaches. Disease activity was assessed using the Gastrointestinal Symptom Rating Scale.

Results: Serum metabolome significantly differed between CD patients, UC patients, and HC individuals. The metabolomic differences of UC and CD patients compared with HC individuals were more pronounced than the differences between UC and CD patients. Differences in serum levels of pyruvic acid, histidine, and the branched-chain amino acids leucine and valine were detected. The size of low-density lipoprotein particles shifted from large to small dense particles in patients with CD. Of note, apolipoprotein A1 and A2 serum levels were decreased in CD and UC patients with higher fecal calprotectin levels. The Gastrointestinal Symptom Rating Scale is negatively associated with the concentration of apolipoprotein A2.

Conclusions: Metabolomic assessment of serum samples facilitated the differentiation of IBD patients and HC individuals. These differences were constituted by changes in amino acid and lipoprotein levels. Furthermore, disease activity in IBD patients was associated with decreased levels of the atheroprotective apolipoproteins A1 and A2.

Keywords: IBD; amino acids; apolipoprotein; biomarker; lipoprotein; metabolomics; nuclear magnetic resonance spectroscopy.

Plain language summary

The metabolic and lipidomic serum profile of patients with inflammatory bowel disease was analyzed using proton nuclear magnetic resonance spectroscopy. A significantly altered profile in comparison with healthy control individuals was identified, characterized by more atherogenic properties.