P0019 Investigation of the serum sphingolipid and ceramide profile in patients with Crohn's disease at different stages of the disease
Authors: Kubesch A , Neumann E , Mohs K , Gurke R , Zeuzem S , Blumenstein I 
Published: January 2025

Abstract

Background
Ceramides and sphingolipids are components of the cell membrane of the intestinal epithelium and contribute to the integrity of the intestinal barrier (1, 2). The expression of specific sphingolipid and ceramide subgroups can vary depending on the inflammatory activity of Inflammatory bowel diseases (IBD) and may influence the course of the disease. A distinct lipid profile was shown for ulcerative colitis compared to healthy subjects and different expression depending on disease activity. Less data is available for Crohn's disease (CD) (3).
In this study, patients with MC at different stages of the disease were to be analysed with regard to their sphingolipid and ceramide profile using liquid chromatography tandem mass spectrometry (LC-MS/MS). The aim was to identify biomarkers that correlate with inflammatory activity so that they can be used in diagnostics and therapeutic monitoring. They could also serve as a target for a new therapeutic approach.

Methods
Patients who were experienced in therapy and had relevant disease activity at the time of blood sampling were included in the study after receiving a positive ethics vote. Patients were considered as treatment-experienced if they had received at least 2 prior biologic therapies. Disease activity was defined by clinical activity indices (Harvey-Bradshaw index &gt;/= 4) and faecal calprotectin (&gt;/= 250 ug/g). Further inclusion criteria were: Age of majority, a &gt;3 month diagnosis of Crohn's disease and written informed consent.
Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to quantify the sphingolipids in plasma. The analytes were extracted using liquid-liquid extraction and measured using two different LC-MS/MS methods for sphingolipids and ceramides.

Results
In the comparison between the Crohn's disease and the control cohort, there were significant differences for the ceramides Cer d18:1/16:0 (p=0.009), Cer d 18.1/18:0 (p=0.025) and Cer 18.1/24:0 (p=0.035) showed higher concentrations in the MC group. For the lactosylceramides, there were significant group differences for LacCer 18:1/16:0 (p=0.005) and LacCer 18.1/18:0 (p=0.009). For sphingosine-1-phosphatase, there were significant differences for S1P 16:0 (p&lt;0.001). LacCer and S1P concentrations were also higher in the MC group.

Conclusion
In the present study, a distinct difference in individual sphingolipid and ceramide concentrations could be determined in patients with Crohn's disease under an advanced therapy line and relevant disease activity compared to a control group. Overall, the concentrations in the MC group were higher in the significantly different parameters. Overall, the data on the role of sphingolipids and ceramides in IBD is not yet conclusive and further research is warranted.

References
1.Cancers 2024, 16, 789. https://doi.org/10.3390/cancers16040789Biomolecules 2020, 10, 1083.
2.Espinoza KS, Snider AJ. Therapeutic Potential for Sphingolipids in Inflammatory Bowel Disease and Colorectal Cancer. Cancers (Basel). 2024 Feb 15;16(4):789. doi: 10.3390/cancers16040789. PMID: 38398179; PMCID: PMC10887199.
3.Filimoniuk, A.; Blachnio-Zabielska, A.; Imierska, M.; Lebensztejn, D.M.; Daniluk, U. Sphingolipid Analysis Indicate Lactosylceramide as a Potential Biomarker of Inflammatory Bowel Disease in Children. Biomolecules 2020, 10, 1083. https://doi.org/10.3390/biom10071083