Assessment of trimethylamine-N-oxide at the blood-cerebrospinal fluid barrier

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 (QALB) and TMAO (QTMAO) quotient and evaluating QTMAO values in individuals with and without blood-CSF barrier dysfunction. A total of 290 patients, who underwent diagnostic lumbar puncture with QALB and QTMAO 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 QALB was significantly associated with the QTMAO (ß-coefficient = 0.312; p < 0.001). A total of 117 patients with blood-CSF barrier dysfunction had significantly higher median (Q1 – Q3) QTMAO 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. QALB showed a relevant influence on QTMAO. Present results indicate that TMAO may cross the blood-CSF barrier.