Metabolomic Characterization of Cerebrospinal Fluid from Intracranial Bacterial Infection Pediatric Patients: A Pilot Study.

Yiwen Wang,Yu Liu,Ruoping Chen,Liang Qiao

doi:10.3390/molecules26226871

Abstract

Intracranial bacterial infection remains a major cause of morbidity and mortality in neurosurgical cases. Metabolomic profiling of cerebrospinal fluid (CSF) holds great promise to gain insights into the pathogenesis of central neural system (CNS) bacterial infections. In this pilot study, we analyzed the metabolites in CSF of CNS infection patients and controls in a pseudo-targeted manner, aiming at elucidating the metabolic dysregulation in response to postoperative intracranial bacterial infection of pediatric cases. Untargeted analysis uncovered 597 metabolites, and screened out 206 differential metabolites in case of infection. Targeted verification and pathway analysis filtered out the glycolysis, amino acids metabolism and purine metabolism pathways as potential pathological pathways. These perturbed pathways are involved in the infection-induced oxidative stress and immune response. Characterization of the infection-induced metabolic changes can provide robust biomarkers of CNS bacterial infection for clinical diagnosis, novel pathways for pathological investigation, and new targets for treatment.

Highlights

Cerebrospinal fluid (CSF), the biofluid circulating from the choroid plexus toward the lumbar sac and venous blood, carries abundant information regarding the metabolic and transport state of the central neural system (CNS) [1,2]
Laarhoven et al measured the metabolome of cerebrospinal fluid (CSF) from patients with tuberculous meningitis using a liquid chromatography mass spectrometry (LC-MS) platform and suggested tryptophan as a predictor of survival [19]
In the function prediction stage, pathway analysis related our experimental results with prior curation, broadening the biological picture regarding the intracranial bacterial infection of pediatric patients

Summary

Introduction

Cerebrospinal fluid (CSF), the biofluid circulating from the choroid plexus toward the lumbar sac and venous blood, carries abundant information regarding the metabolic and transport state of the central neural system (CNS) [1,2]. Multi-omics characterization of CSF has curated a sum of ~250 miRNAs, ~3400 proteins, ~900 peptides and ~440 metabolites [4,5,6,7,8]. The multi-omics profiling of cerebrospinal fluid (CSF) holds great promise to gain insights into CNS diseases, including neurodegeneration [9], brain tumor [10], brain injury [11], and CNS infection [12]. To elucidate the mechanism of the pathogenesis, multi-platform characterization of CSF from intracranial bacterial infection patients has been performed. Quist-Paulsen et al further profiled CSF metabolites in the tryptophan metabolism pathway and cytokines across patients with CNS bacterial infection and autoimmune neuroinflammation, and reported an IFN-γ mediated up-regulation in tryptophan metabolism in case of bacterial meningitis [20]. The inflammatory CNS profile was different between pediatric cases and adult patients, including a lower elevated level of protein and white blood count, and a higher elevated level of aspartate transaminase in pediatric cases [21]

Methods

Results

Conclusion