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Clinical Trial
. 2020 Mar 14;12(3):765.
doi: 10.3390/nu12030765.

Plasma Levels of the Bioactive Sphingolipid Metabolite S1P in Adult Cystic Fibrosis Patients: Potential Target for Immunonutrition?

Emina Halilbasic  1 , Elisabeth Fuerst  2 , Denise Heiden  2 , Lukasz Japtok  3 , Susanne C Diesner  4 , Michael Trauner  1 , Askin Kulu  5 , Peter Jaksch  5 , Konrad Hoetzenecker  5 , Burkhard Kleuser  3 , Lili Kazemi-Shirazi  1 , Eva Untersmayr  2
Affiliations
Clinical Trial

Plasma Levels of the Bioactive Sphingolipid Metabolite S1P in Adult Cystic Fibrosis Patients: Potential Target for Immunonutrition?

Emina Halilbasic et al. Nutrients. .

Abstract

Recent research has linked sphingolipid (SL) metabolism with cystic fibrosis transmembrane conductance regulator (CFTR) activity, affecting bioactive lipid mediator sphingosine-1-phosphate (S1P). We hypothesize that loss of CFTR function in cystic fibrosis (CF) patients influenced plasma S1P levels. Total and unbound plasma S1P levels were measured in 20 lung-transplanted adult CF patients and 20 healthy controls by mass spectrometry and enzyme-linked immunosorbent assay (ELISA). S1P levels were correlated with CFTR genotype, routine laboratory parameters, lung function and pathogen colonization, and clinical symptoms. Compared to controls, CF patients showed lower unbound plasma S1P, whereas total S1P levels did not differ. A positive correlation of total and unbound S1P levels was found in healthy controls, but not in CF patients. Higher unbound S1P levels were measured in ΔF508-homozygous compared to ΔF508-heterozygous CF patients (p = 0.038), accompanied by higher levels of HDL in ΔF508-heterozygous patients. Gastrointestinal symptoms were more common in ΔF508 heterozygotes compared to ΔF508 homozygotes. This is the first clinical study linking plasma S1P levels with CFTR function and clinical presentation in adult CF patients. Given the emerging role of immunonutrition in CF, our study might pave the way for using S1P as a novel biomarker and nutritional target in CF.

Keywords: cystic fibrosis; high density lipoproteins; immunonutrition; intestine; sphingolipids; sphingosine-1-phosphate; ΔF508 mutation.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Plasma levels of total and unbound sphingosine-1-phosphate (S1P) in CF patients compared to healthy controls. Total S1P levels were measured by liquid chromatography (LC)–mass spectrometry (A), unbound S1P by ELISA (B). Significantly lower unbound S1P levels were found in CF patients compared to healthy controls after the exclusion of two statistical outliers (B). A positive correlation of unbound with total S1P levels was found for healthy controls (C), but not for CF patients (D). * p < 0.05.
Figure 2
Figure 2
Correlation of S1P levels with hemoglobin and triglycerides in CF patients. No correlation was observed for total S1P levels measured by liquid chromatography mass spectrometry (LC–MS) with hemoglobin (A) and triacylglycerols (TG) (C). Positive correlation with hemoglobin (B) and TG (D) was found for unbound S1P titers measured by ELISA in the CF patients.
Figure 3
Figure 3
Higher unbound S1P levels in ∆F508-homozygous compared to ∆F508-heterozygous CF patients. No difference in total S1P levels measured by LC–MS was observed between ∆F508-homozygous and -heterozygous CF patients (A). Unbound S1P titers measured by ELISA were significantly higher in ΔF508-homozygous CF patients compared to ΔF508-heterozygous patients (B). A higher number of ΔF508-heterozygous CF patients had GI symptoms at time-point of S1P measurement compared to ΔF508-homozygous patients (C).
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