The Gut Microbial Metabolite Trimethylamine-N-Oxide Is Present in Human Cerebrospinal Fluid

Abstract

Trimethylamine-N-oxide (TMAO) is a small organic molecule, derived from the intestinal and hepatic metabolism of dietary choline and carnitine. Although the involvement of TMAO in the framework of many chronic diseases has been recently described, no evidence on its putative role in the central nervous system has been provided. The aim of this study was to evaluate whether TMAO is present at detectable levels in human cerebrospinal fluid (CSF). CSF was collected for diagnostic purposes from 58 subjects by lumbar puncture and TMAO was quantified by using liquid chromatography coupled with multiple-reaction monitoring mass spectrometry. The molecule was detected in all samples, at concentrations ranging between 0.11 and 6.43 µmol/L. Further analysis on CSF revealed that a total of 22 subjects were affected by Alzheimer’s disease (AD), 16 were affected by non-AD related dementia, and 20 were affected by other neurological disorders. However, the stratification of TMAO levels according to the neurological diagnoses revealed no differences among the three groups. In conclusion, we provide the first evidence that TMAO can be assessed in human CSF, but the actual impact of this dietary metabolite in the patho-physiolgy of the central nervous system requires further study.

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

“…In a murine cohort, serum TMAO was connected to the process of brain aging (Li et al, 2018[ 8 ]). Recently, it was shown that TMAO is also present in the human cerebrospinal fluid (CSF) (Del Rio et al, 2017[ 4 ]). Individuals with Alzheimer's disease were observed with elevated CSF TMAO concentrations (Vogt et al, 2018[ 21 ]).…”

The Microbiome and the Gut‐Liver‐Brain Axis for Central Nervous System Clinical Pharmacology: Challenges in Specifying and Integrating In Vitro and In Silico Models

“…The clinical penetration of TMAO across the BBB was unknown at the time of the study, and 26% of the TMAO penetrated the NVU. 119 The significance of this study was that TMAO's penetration of the BBB was subsequently confirmed clinically by the analysis of spinal-tap fluid from > 50 patients, 129 constituting what is believed to be the first MPS prediction later confirmed in humans.…”

The Microbiota–Gut–Brain Axis–Heart Shunt Part II: Prosaic Foods and the Brain–Heart Connection in Alzheimer Disease

“…It was shown that TMANO lowers the critical concentration of tubulin needed for tubulin assembly by modulating binding of protein kinase A-phosphorylated microtubule-associated protein tau to form tubulin. It seems that TMANO levels are not related to neurological disorders [76]. However, since one hallmark of AD is hyper-phosphorylation of the microtubule-associated protein Tau, this finding offers a therapeutic implication for TMANO in Alzheimer disease.…”