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The Gut Microbial Metabolite Trimethylamine-N-Oxide Is Present in Human Cerebrospinal Fluid
Daniele Del Rio1, Francesca Zimetti2, Paolo Caffarra3
1Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy. daniele.delrio@unipr.it.
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.
Insights
Trimethylamine-N-oxide (TMAO) is detectable in human cerebrospinal fluid (CSF). This study found TMAO in all CSF samples, but its levels did not differ between neurological disease groups.
Area of Science:
- Neuroscience
- Metabolomics
- Clinical Chemistry
Background:
- Trimethylamine-N-oxide (TMAO) is a metabolite from dietary choline and carnitine.
- TMAO's role in chronic diseases is known, but its central nervous system involvement is unstudied.
- Investigating TMAO in human cerebrospinal fluid (CSF) is crucial for understanding its neurological impact.
Purpose of the Study:
- To determine if TMAO is detectable in human CSF.
- To quantify TMAO levels in CSF samples from individuals with neurological disorders.
- To explore potential correlations between TMAO levels and specific neurological conditions.
Main Methods:
- CSF samples were collected via lumbar puncture from 58 subjects.
- TMAO concentrations were measured using liquid chromatography-mass spectrometry (LC-MS/MS).
- Subjects were categorized into Alzheimer's disease, non-AD dementia, and other neurological disorders groups.
Main Results:
- TMAO was detected in all analyzed CSF samples.
- CSF TMAO concentrations ranged from 0.11 to 6.43 µmol/L.
- No significant differences in TMAO levels were observed across the different neurological diagnosis groups.
Conclusions:
- This study provides the first evidence of TMAO detectability in human CSF.
- The findings establish a baseline for TMAO levels in human CSF.
- Further research is needed to elucidate the precise role of TMAO in central nervous system pathophysiology.
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