Relationship between Metabolomics Profile of Perilymph in Cochlear-Implanted Patients and Duration of Hearing Loss.

Trinh Trinh,Andres Andres,Blasco Blasco,Emond Emond,Lefevre Lefevre,Bakhos Bakhos,Lescanne Lescanne

doi:10.3390/metabo9110262

Abstract

Perilymph metabolomic analysis is an emerging innovative strategy to improve our knowledge of physiopathology in sensorineural hearing loss. This study aims to develop a metabolomic profile of human perilymph with which to evaluate the relationship between metabolome and the duration of hearing loss. Inclusion criteria were eligibility for cochlear implantation and easy access to the round window during surgery; patients with residual acoustic hearing in the ear to be implanted were excluded. Human perilymph was sampled from 19 subjects during cochlear implantation surgery. The perilymph analysis was performed by Liquid Chromatography−High-Resolution Mass and data were analyzed by supervised multivariate analysis based on Partial Least-Squares Discriminant Analysis and univariate analysis. Samples were grouped according to their median duration of hearing loss. We included the age of patients as a covariate in our models. Statistical analysis and pathways evaluation were performed using Metaboanalyst. Nineteen samples of human perilymph were analyzed, and a total of 106 different metabolites were identified. Metabolomic profiles were significantly different for subjects with ≤12 or >12 years of hearing loss, highlighting the following discriminant compounds: N-acetylneuraminate, glutaric acid, cystine, 2-methylpropanoate, butanoate and xanthine. As expected, the age of patients was also one of the main discriminant parameters. Metabolic signatures were observed for duration of hearing loss. These findings are promising steps towards illuminating the pathophysiological pathways associated with etiologies of sensorineural hearing loss, and hold open the possibilities of further explorations into the mechanisms of sensorineural hearing loss using metabolomic analysis.

Highlights

Sensorineural hearing loss (SNHL) can negatively affect the development of spoken language, education and social interactions, can reduce quality of life, and limit human communication and socio-professional relations [1]
The objective of this study was to describe the metabolomic profile of perilymph extracted from patients with SNHL during cochlear implants (CIs) surgery
No outliers were identified on the Principal Component Analysis (PCA) score plot for quality control samples and patients

Summary

Introduction

Sensorineural hearing loss (SNHL) can negatively affect the development of spoken language, education and social interactions, can reduce quality of life, and limit human communication and socio-professional relations [1]. Around 5% of the worldwide population suffers from different degrees of hearing loss [2], and SNHL is the most common sensory deficit in more developed countries [3,4]. Metabolites 2019, 9, 262 patients with severe-to-profound SNHL who receive no benefit from hearing aids, cochlear implants (CIs) can partially restore hearing by electrically stimulating the surviving auditory nerve fibers [8]. The etiology of SNHL may be evident for some patients, progressive hearing loss remains an enigma. SNHL may be caused by damage to approximately 30 different cell types, and by alteration of the cochlear nerves. From a histological point of view, the most common mechanism is hair cell (HC) loss and damage to the spiral ganglion neurons (SGNs)

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