Assessment of trimethylamine-N-oxide at the blood-cerebrospinal fluid barrier: Results from 290 lumbar punctures

Dietmar Enko; Sieglinde Zelzer; Tobias Niedrist; Sandra Holasek; Andreas Baranyi; Wolfgang J Schnedl; Markus Herrmann; Andreas Meinitzer

doi:10.17179/excli2020-2763

Assessment of trimethylamine-N-oxide at the blood-cerebrospinal fluid barrier: Results from 290 lumbar punctures

EXCLI J. 2020 Sep 9:19:1275-1281. doi: 10.17179/excli2020-2763. eCollection 2020.

Authors

Dietmar Enko^{1

2}, Sieglinde Zelzer¹, Tobias Niedrist¹, Sandra Holasek³, Andreas Baranyi⁴, Wolfgang J Schnedl⁵, Markus Herrmann¹, Andreas Meinitzer¹

Affiliations

¹ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
² Institute of Clinical Chemistry and Laboratory Medicine, General Hospital Hochsteiermark, Leoben, Austria.
³ Department of Immunology and Pathophysiology, Medical University of Graz, Otto Loewi Research Center, Graz, Austria.
⁴ Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.
⁵ Practice for General Internal Medicine, Bruck/Mur, Austria.

Abstract

Recently, the microbiome-derived trimethylamine-N-oxide (TMAO) was shown to be present in human cerebrospinal fluid (CSF). However, data on the potential of TMAO crossing the blood-CSF barrier are still lacking. This retrospective study aimed at investigating possible associations between the CSF/serum albumin (Q_ALB) and TMAO (Q_TMAO) quotient and evaluating Q_TMAO values in individuals with and without blood-CSF barrier dysfunction. A total of 290 patients, who underwent diagnostic lumbar puncture with Q_ALB and Q_TMAO determination, were evaluated. Serum and CSF TMAO measurements were performed on a tandem mass spectrometry SCIEX QTRAP 4500 (Applied Biosystems, Framingham, MA, USA) coupled with an Agilent 1260 Infinity HPLC system (Agilent Technologies Santa Clara, CA, USA). Serum and CSF albumin were measured on the Atellica^® NEPH 630 system (Siemens Healthineers, Erlangen, Germany). CSF TMAO levels were positively correlated with serum TMAO levels (ρ = 0.709, p < 0.001). The Q_ALB was significantly associated with the Q_TMAO (ß-coefficient = 0.312; p < 0.001). A total of 117 patients with blood-CSF barrier dysfunction had significantly higher median (Q1 - Q3) Q_TMAO values (4.7 (2.8 - 7.5) vs. 3.8 (2.5 - 5.7) x 10^-1, p = 0.002) compared to 173 individuals with normal blood-CSF barrier function. CSF and serum TMAO concentrations were significantly associated in 290 CSF/serum pairs from lumbar punctures of clinical routine. Q_ALB showed a relevant influence on Q_TMAO. Present results indicate that TMAO may cross the blood-CSF barrier.

Keywords: biomarkers; blood-cerebrospinal fluid barrier; liquid chromatography-tandem mass spectrometry; trimethylamine-N-oxide.