Metabolomic Studies in Inner Ear Pathologies

Boullaud, L.; Blasco, Hélène; Trinh, Thuy-Trân; Bakhos, D.

doi:10.3390/metabo12030214

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…This study substantially augments the scarce literature on plasma metabolomic biomarkers for tinnitus. Specifically, a few small metabolomic investigations of sensorineural hearing loss in animals and humans have examined metabolomic profiles in perilymph, plasma, urine, temporal bone or brain tissue, and evaluated metabolomic alterations after noise or cisplatin exposure. Plasma metabolomic alterations after noise exposure were observed for several individual metabolites and pathways, such as those involving glycerophospholipid, choline, and fatty acid metabolism .…”

Section: Discussionmentioning

confidence: 99%

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Association of Plasma Metabolomic Biomarkers With Persistent Tinnitus

Zeleznik

Welling

Stanković

et al. 2023

JAMA Otolaryngol Head Neck Surg

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ImportancePersistent tinnitus is common, disabling, and difficult to treat.ObjectiveTo evaluate the association between circulating metabolites and persistent tinnitus.Design, Setting, and ParticipantsThis was a population-based case-control study of 6477 women who were participants in the Nurses’ Health Study (NHS) and NHS II with metabolomic profiles and tinnitus data. Information on tinnitus onset and frequency was collected on biennial questionnaires (2009-2017). For cases, metabolomic profiles were measured (2015-2021) in blood samples collected after the date of the participant’s first report of persistent tinnitus (NHS, 1989-1999 and 2010-2012; NHS II, 1996-1999). Data analyses were performed from January 24, 2022, to January 14, 2023.ExposuresIn total, 466 plasma metabolites from 488 cases of persistent tinnitus and 5989 controls were profiled using 3 complementary liquid chromatography tandem mass spectrometry approaches.Main Outcomes and MeasuresLogistic regression was used to estimate odds ratios (ORs) of persistent tinnitus (per 1 SD increase in metabolite values) and 95% CIs for each individual metabolite. Metabolite set enrichment analysis was used to identify metabolite classes enriched for associations with tinnitus.ResultsOf the 6477 study participants (mean [SD] age, 52 [9] years; 6477 [100%] female; 6121 [95%] White individuals) who were registered nurses, 488 reported experiencing daily persistent (≥5 minutes) tinnitus. Compared with participants with no tinnitus (5989 controls), those with persistent tinnitus were slightly older (53.0 vs 51.8 years) and more likely to be postmenopausal, using oral postmenopausal hormone therapy, and have type 2 diabetes, hypertension, and/or hearing loss at baseline. Compared with controls, homocitrulline (OR, 1.32; (95% CI, 1.16-1.50); C38:6 phosphatidylethanolamine (PE; OR, 1.24; 95% CIs, 1.12-1.38), C52:6 triglyceride (TAG; OR, 1.22; 95% CIs, 1.10-1.36), C36:4 PE (OR, 1.22; 95% CIs, 1.10-1.35), C40:6 PE (OR, 1.22; 95% CIs, 1.09-1.35), and C56:7 TAG (OR, 1.21; 95% CIs, 1.09-1.34) were positively associated, whereas α-keto-β-methylvalerate (OR, 0.68; 95% CIs, 0.56-0.82) and levulinate (OR, 0.60; 95% CIs, 0.46-0.79) were inversely associated with persistent tinnitus. Among metabolite classes, TAGs (normalized enrichment score [NES], 2.68), PEs (NES, 2.48), and diglycerides (NES, 1.65) were positively associated, whereas phosphatidylcholine plasmalogens (NES, −1.91), lysophosphatidylcholines (NES, −2.23), and cholesteryl esters (NES,−2.31) were inversely associated with persistent tinnitus.Conclusions and RelevanceThis population-based case-control study of metabolomic profiles and tinnitus identified novel plasma metabolites and metabolite classes that were significantly associated with persistent tinnitus, suggesting that metabolomic studies may help improve understanding of tinnitus pathophysiology and identify therapeutic targets for this challenging disorder.

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Section: Discussionmentioning

confidence: 99%

“…Data analyses were performed from January 24, 2022, to January 14, 2023, using R, version 4.0.3 (R Foundation for Statistical Computing) and the R packages, Stats, Fast Gene Set Enrichment Analysis, 25 and ggplot2. 26…”

Section: Discussionmentioning

confidence: 99%

Association of Plasma Metabolomic Biomarkers With Persistent Tinnitus

Zeleznik

Welling

Stanković

et al. 2023

JAMA Otolaryngol Head Neck Surg

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“…Our study substantially augments the currently scarce literature on plasma metabolomic biomarkers for tinnitus. Specifically, a few small metabolomic investigations of sensorineural hearing loss in animals and humans have examined metabolomic profiles in perilymph, plasma, urine, temporal bone or brain tissue, 33 and evaluated metabolomic alterations following noise or cisplatin exposure. Plasma metabolomic alterations following noise exposure were observed for several individual metabolites and pathways, such as those involving glycerophospholipid, choline and fatty acid metabolism.…”

Section: Discussionmentioning

confidence: 99%

A Population-Based Study of Plasma Metabolomic Profiles of Persistent Tinnitus Identifies Candidate Biomarkers

Zeleznik

Welling

Stanković

et al. 2022

Preprint

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Tinnitus, the perception of sound without the corresponding external stimulus, currently affects 15% of the US population. There is a critical need to unravel the heterogeneous etiologies underlying tinnitus and identify tailored treatment targets. Metabolomic studies have elucidated biological pathways underlying several neurodegenerative disorders and could identify metabolic perturbations that influence tinnitus development. We conducted the first large-scale metabolomic study to identify novel tinnitus biomarkers. We cross-sectionally evaluated plasma metabolite profiles and persistent tinnitus among 6477 women (488 with daily tinnitus ≥5 minutes and 5989 controls). A broad array of 466 metabolites was measured using liquid-chromatography mass spectrometry. Logistic regression was used to estimate odds ratios (OR, per 1 SD increase in metabolite values) and 95% confidence intervals (CI) for each individual metabolite while Metabolite Set Enrichment Analysis (MSEA) was used to identify metabolite classes enriched for associations with tinnitus; all models were adjusted for multiple comparisons. Compared with controls, homocitrulline (OR(95%CI)=1.32(1.16-1.50), C38:6 phosphatidylethanolamine (PE; 1.24(1.12-1.38)), C52:6 triglyceride (TAG; 1.22(1.10-1.36)), C36:4 PE (1.22(1.1-1.35)), C40:6 PE (1.22(1.09-1.35)), and C56:7 TAG (1.21(1.09-1.34)) were positively associated, whereas alpha-keto-beta-methylvalerate (0.68(0.56-0.82)) and levulinate (0.60(0.46-0.79)) were inversely associated with tinnitus (adjusted-p<0.05). Among metabolite classes, TAGs, PEs, and diglycerides (DAGs) were positively associated, while phosphatidylcholine (PC) plasmalogens, lysophosphatidylcholines (LPC), and cholesteryl esters were inversely associated with tinnitus (false discovery rate <0.05). This study identified novel plasma metabolites and metabolite classes that were significantly associated with persistent tinnitus. These findings extend our current understanding of tinnitus and could inform investigations of therapeutic targets for this challenging disorder.

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“…However, biological fluids of the organism rather than tissues are most often used for searching for characteristic metabolites in pathologies. For example, in the review [4], devoted to metabolic studies in pathologies of the inner ear, the main objects of research were blood, urine, and perilymph. Only in two of the thirteen works selected for the review were the studies performed on fluids: in one of them (on rats), metabolic changes were investigated in cerebral tissue after acoustic trauma, and in the other (on mice), metabolic changes were examined in the temporal bone at noise-induced hearing loss.…”

Section: Introductionmentioning

confidence: 99%

Novel Approaches in the Diagnostics of Ear-Nose-Throat Diseases Using High-Resolution THz Spectroscopy

et al. 2023

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Nowadays, physicochemical methods of analysis are used in medical diagnostics. One can identify metabolites characteristic of a particular disease. The compilation of a metabolic profile will facilitate the diagnosis of diseases, evaluate their stage and etiology, and predict treatment. The goal of the study is to analyze the metabolite composition of the ear-nose-throat (ENT) tissues by high-resolution THz spectroscopy based on nonstationary effects and compare metabolites formed during the thermal decomposition of relatively healthy mucosa, polyps, and cysts. Studies were performed with the spectrometers operating from 118 to 178 GHz. The chemical compounds were identified using online catalogs. In all samples, there are such substances as methanol, propanediol, acetaldehyde, acetonitrile, butyronitrile, methyl mercaptan, azole, ethylene sulfide, carbon sulfide, and sulfur dioxide. In the spectrum of relatively healthy mucosa, the number of absorption lines of these substances is much less than in the spectrum of the polyps and cysts, which indicates their lower concentration. In the products of the polyps and cysts, acetone, hydroxyacetone, dihydroxyacetone, propionitrile, acrylonitrile, aminopropionitrile, hydroxyacetonitrile, aminoacetonitrile, methylbutironitrile, propanal, glycolaldehyde, lactaldehyde, and malone dialdehyde appear. The products of cysts’ thermal decomposition also contain acetic and acrylic acids. High-resolution THz spectroscopy has been shown to be promising for detecting disease metabolites in ENT tissues.

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Metabolomic Studies in Inner Ear Pathologies

Cited by 7 publications

References 36 publications

Association of Plasma Metabolomic Biomarkers With Persistent Tinnitus

Association of Plasma Metabolomic Biomarkers With Persistent Tinnitus

A Population-Based Study of Plasma Metabolomic Profiles of Persistent Tinnitus Identifies Candidate Biomarkers

Novel Approaches in the Diagnostics of Ear-Nose-Throat Diseases Using High-Resolution THz Spectroscopy

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