Using CE-MS and LC-MS to Profile Mouth-Rinse Metabolites for Rapid Workplace Stress Assessment

Because occupational stress impacts employee well-being and performance, there is a critical need for rapid, non-invasive, and objective assessment techniques.. In response, a recent study investigated the potential of metabolite profiling of mouth-rinsed water (MW)-an oral biofluid collected in just 10 s-as a screening tool for psychophysiological stress among office workers, with biochemical features profiled using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry (LC-MS). A paper presenting the findings of the study was published in Scientific Reports.¹

A major contributor to both mental and physical health issues, including depression and cardiovascular disease, stress can significantly reduce workplace productivity, which leads to substantial economic losses for both individuals and the organizations that employ them.² The accurate and objective assessment of stress, therefore, is crucial. While a variety of screening methods, including questionnaires and salivary biomarkers, have been proposed, both offer advantages and disadvantages.Achieving a balance of objectivity, accuracy, and convenience therefore remains a challenge.^3,4

Researchers often use saliva to measure stress because it is a painless way to get real data, rather than just relying on how people answer surveys. However, it takes about five minutes to collect a sample, which slows things down too much when testing large groups of people. In addition, the makeup of our saliva naturally changes depending on the time of day, which makes it harder to get straightforward and accurate results.^4,5Using a 10-second mouth rinse is a faster, easier alternative to collecting saliva. It works just as effectively at capturing unique personal details, including chemical changes related to a person's sex or their daily body clock.^6,7

Thirty-two participants were classified into high-stress and control groups for this study, based on the State-Trait Anxiety Inventory and the Brief Job Stress Questionnaire, and objective physiological measures. MW samples were collected at four time points, including before and after short mental stress tasks.¹

A total of 559 analytes, including 532 water-soluble metabolites, 25 steroids, and 2 salivary proteins, were measured, of which 127 analytes with acceptable analytical precision were selected for subsequent analyses. Statistically significant differences in numerous metabolites indicated stress-associated alterations in metabolic activity. Notably, a predictive model using the ratio of N-acetyl-β-alanine to asymmetric dimethylarginine achieved high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.845 for identifying high stress. The distinct metabolite dynamics under varying stress conditions suggest multiple stress-response mechanisms.¹

“These findings,” write the authors of the paper,¹ “underscore MW metabolite profiling as a promising approach for assessing and managing workplace stress.”

The researchers admit that further research is needed to clarify the biological significance of these findings, specifically large-scale clinical studies to validate the effectiveness of these biomarkers.¹

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References

1. Maruyama, Y.; Yamada, K.; Inokuchi, T. et al. Metabolomics of Mouth-Rinsed Water for Assessing Psychophysiological Stress in Office Workers. Sci Rep. 2026.DOI: 10.1038/s41598-026-42241-4
2. Piao, X.; Xie, J.; Managi, S. Continuous Worsening of Population Emotional Stress Globally: Universality and Variations. BMC Public Health 2024, 24 (1), 3576. DOI: 10.1186/s12889-024-20961-4
3. Breedvelt, J. J. F.; Zamperoni, V.; South, E. et al. A Systematic Review of Mental Health Measurement Scales for Evaluating the Effects of Mental Health Prevention Interventions. Eur J Public Health 2020, 30 (3), 539-545. DOI: 10.1093/eurpub/ckz233
4. Chojnowska, S.; Ptaszyńska-Sarosiek, I.; Kępka, A. et al. Salivary Biomarkers of Stress, Anxiety and Depression. J Clin Med. 2021, 10 (3), 517. DOI: 10.3390/jcm10030517
5. Kawanishi, N.; Hoshi, N.; Masahiro, S. et al. Effects of Inter-Day and Intra-Day Variation on Salivary Metabolomic Profiles. Clin Chim Acta 2019, 489, 41-48. DOI: 10.1016/j.cca.2018.11.030
6. Maruyama, Y.; Nishimoto, Y.; Umezawa, K. et al. Comparison of Oral Metabolome Profiles of Stimulated Saliva, Unstimulated Saliva, and Mouth-Rinsed Water. Sci Rep. 2022, 12 (1), 689. DOI: 10.1038/s41598-021-04612-x
7. Maruyama, Y.; Fujii, N.; Kawamata, R. et al. Intra- and Inter-Day Variations in Oral Metabolites from Mouth-Rinsed Water Determined Using Capillary Electrophoresis-Mass Spectrometry Metabolomics. Clin Chim Acta 2025, 565, 119965. DOI: 10.1016/j.cca.2024.119965