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. 2024 Jun 4:11:1334865.
doi: 10.3389/fmed.2024.1334865. eCollection 2024.

Distinct metabolomic and lipidomic profiles in serum samples of patients with primary sclerosing cholangitis

Tanja Fererberger  1 , Christa Buechler  1 , Arne Kandulski  1 , Tanja Elger  1 , Johanna Loibl  1 , Stephan Schmid  1 , Stefanie Sommersberger  1 , Stefan Gunawan  1 , Sebastian Zundler  2   3 , Muriel Huss  1 , Dominik Bettenworth  4   5 , Sally Kempa  6 , Simon Weidlich  7 , Bandik Föh  8   9 , Xinyu Huang  10 , Marcin Grzegorzek  10 , Stefanie Derer-Petersen  8 , Ulrich L Günther  11 , Jens U Marquardt  9 , Claudia Kunst  1 , Karsten Gülow  1 , Martina Müller  1 , Christian Sina  8   9   12 , Franziska Schmelter  8 , Hauke C Tews  1
Affiliations

Distinct metabolomic and lipidomic profiles in serum samples of patients with primary sclerosing cholangitis

Tanja Fererberger et al. Front Med (Lausanne). .

Abstract

Intoduction: Identification of specific metabolome and lipidome profile of patients with primary sclerosing cholangitis (PSC) is crucial for diagnosis, targeted personalized therapy, and more accurate risk stratification.

Methods: Nuclear magnetic resonance (NMR) spectroscopy revealed an altered metabolome and lipidome of 33 patients with PSC [24 patients with inflammatory bowel disease (IBD) and 9 patients without IBD] compared with 40 age-, sex-, and body mass index (BMI)-matched healthy controls (HC) as well as 64 patients with IBD and other extraintestinal manifestations (EIM) but without PSC.

Results: In particular, higher concentrations of pyruvic acid and several lipoprotein subfractions were measured in PSC in comparison to HC. Of clinical relevance, a specific amino acid and lipid profile was determined in PSC compared with IBD and other EIM.

Discussion: These results have the potential to improve diagnosis by differentiating PSC patients from HC and those with IBD and EIM.

Keywords: IBD; NMR; PSC; lipidome; metabolome.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) Scores plot of PLS-DA for quantified NMR data in patients with PSC (red, n = 33), EIM (blue, n = 64), and HC (green, n = 40). (B) Corresponding loadings plot of distinct metabolome and lipidome profiles. Axis label: latent variable (LV).
FIGURE 2
FIGURE 2
Adjusted forest plot demonstrate the differences of metabolites (A) and lipoproteins (B–I) from PSC (red, n = 33) and EIM (blue, n = 64) compared to HC normalized to the standard deviation of HC. The dashed vertical line indicates the reference values for HC. Statistically significant values of PSC and EIM compared with HC are shown by color-filled circles and squares, and parameters that significantly differed between PSC and EIM are written in bold letters.
FIGURE 3
FIGURE 3
Detailed comparison of altered lipoprotein concentrations in PSC (red, n = 33), EIM (blue, n = 64), and HC (green, n = 40) given as median with 95% confidence interval. The levels of IDL ApoB, IDL particles, and VLDL-4 FC significantly differed between PSC and EIM as well as between PSC and HC. Significant differences determined using the unpaired multiple Mann-Whitney test (p < 0.05) with a false discovery rate of 1% using the method from Benjamini were highlighted (*).
FIGURE 4
FIGURE 4
Detailed comparison of significant altered metabolites and lipoprotein subfractions between PSC (red, n = 33) and HC (green, n = 40), but not in comparison with EIM (blue, n = 64). Concentrations are given as median with 95% confidence interval. The lower limit of detection (LOD) for methionine is 0.05 mmol/L. Significant differences determined using the unpaired multiple Mann-Whitney test (p < 0.05) with a false discovery rate of 1% using the method from Benjamini were highlighted (*).
FIGURE 5
FIGURE 5
Total concentration of pyruvic acid in comparison of PSC (red, n = 33) and HC (green, n = 40). Display of the ROC with an AUC of 0.9068.
See this image and copyright information in PMC

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