Growing evidence suggests that specific volatile organic compound (VOC) profiles may reflect key pathophysiological processes in Parkinson's disease (PD), including alterations in the microbiome, metabolism, and oxidative stress. Identifying reliable VOC biomarkers could enable non-invasive tests for early diagnosis, disease monitoring, and therapy evaluation. This review examines VOC analysis in biological matrices such as breath, skin, and stool, outlining current research and future applications in PD. We evaluate analytical techniques based on sensitivity, specificity, and clinical applicability. Additionally, we classify VOCs identified in previous studies alongside their proposed biological origins. Special attention is given to short-chain fatty acids, produced by the gut microbiome, a novel target in PD research. Our findings highlight the need for larger cohort studies and standardized protocols to advance VOC-based diagnostics in PD. Understanding the interplay between VOCs and PD may facilitate biomarker discovery, enhancing non-invasive diagnostic strategies and personalized disease management.

Department of Brain Sciences Division of Neurology Imperial College London Hammersmith Campus Commonwealth Building London UK

Department of Neurosciences Imperial College London Charing Cross Hospital Fulham Palace Road London UK

Department of Surgery and Cancer Imperial College London Hammersmith Campus Commonwealth Building London UK

J Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences Prague Czech Republic

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Bloem, B. R., Okun, M. S. & Klein, C. Parkinson’s disease. PubMed

Armstrong, M. J. & Okun, M. S. Diagnosis and Treatment of Parkinson Disease: A Review. PubMed

Shahnawaz, M. et al. Development of a Biochemical Diagnosis of Parkinson Disease by Detection of alpha-Synuclein Misfolded Aggregates in Cerebrospinal Fluid. PubMed

Bega, D. et al. Clinical utility of DaTscan in patients with suspected Parkinsonian syndrome: a systematic review and meta-analysis. PubMed PMC

Poewe, W. et al. Parkinson disease. PubMed

None

Belluomo, I. et al. Selected ion flow tube mass spectrometry for targeted analysis of volatile organic compounds in human breath. PubMed

Drabinska, N. et al. A literature survey of all volatiles from healthy human breath and bodily fluids: the human volatilome. PubMed

Le, T. & Priefer, R. Detection technologies of volatile organic compounds in the breath for cancer diagnoses. PubMed

Woodfield, G. et al. Feasibility and acceptability of breath research in primary care: a prospective, cross-sectional, observational study. PubMed PMC

Markar, S. R. et al. Assessment of a Noninvasive Exhaled Breath Test for the Diagnosis of Oesophagogastric Cancer. PubMed PMC

Woodfield, G. et al. Diagnostic performance of a non-invasive breath test for colorectal cancer: COBRA1 study. PubMed

Kamal, F. et al. Virus-induced Volatile Organic Compounds Are Detectable in Exhaled Breath during Pulmonary Infection. PubMed PMC

OwlstoneMedical.

Unger, M. M. et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. PubMed

Cersosimo, M. G. & Benarroch, E. E. Pathological correlates of gastrointestinal dysfunction in Parkinson’s disease. PubMed

Belluomo, I. et al. Combining Thermal Desorption with Selected Ion Flow Tube Mass Spectrometry for Analyses of Breath Volatile Organic Compounds. PubMed PMC

Lawal, O., Ahmed, W. M., Nijsen, T. M. E., Goodacre, R. & Fowler, S. J. Exhaled breath analysis: a review of ‘breath-taking’ methods for off-line analysis. PubMed PMC

Aksenov, A. A. et al. Algorithmic Learning for Auto-deconvolution of GC-MS Data to Enable Molecular Networking within GNPS.

Finberg, J. P. M. et al. Sensor Array for Detection of Early Stage Parkinson’s Disease before Medication. PubMed

Kumari, S. et al. Quantitative metabolomics of saliva using proton NMR spectroscopy in patients with Parkinson’s disease and healthy controls. PubMed

Tisch, U. et al. Detection of asymptomatic nigrostriatal dopaminergic lesion in rats by exhaled air analysis using carbon nanotube sensors. PubMed PMC

Khatib, S. et al. Analysis of volatile organic compounds in rats with dopaminergic lesion: Possible application for early detection of Parkinson’s disease. PubMed

Finberg, J. P. M. et al. Altered Volatile Organic Compound Profile in Transgenic Rats Bearing A53T Mutation of Human alpha-Synuclein: Comparison with Dopaminergic and Serotonergic Denervation. PubMed

Schober, A. Classic toxin-induced animal models of Parkinson’s disease: 6-OHDA and MPTP. PubMed

DuPont, H. L. et al. Fecal microbiota transplantation in Parkinson’s disease-A randomized repeat-dose, placebo-controlled clinical pilot study. PubMed PMC

Sun, M. F. et al. Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson’s disease mice: Gut microbiota, glial reaction and TLR4/TNF-alpha signaling pathway. PubMed

Zhong, Z. et al. Fecal Microbiota Transplantation Exerts a Protective Role in MPTP-Induced Parkinson’s Disease via the TLR4/PI3K/AKT/NF-kappaB Pathway Stimulated by alpha-Synuclein. PubMed

Zhou, Z. L. et al. Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites. PubMed PMC

Dong, X. L. et al. Polymannuronic acid prevents dopaminergic neuronal loss via brain-gut-microbiota axis in Parkinson’s disease model. PubMed

Wang, N. et al. Neuroprotection of chicoric acid in a mouse model of Parkinson’s disease involves gut microbiota and TLR4 signaling pathway. PubMed

Cui, C. et al. Vancomycin Pretreatment on MPTP-Induced Parkinson’s Disease Mice Exerts Neuroprotection by Suppressing Inflammation Both in Brain and Gut. PubMed

Hou, Y. F. et al. Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson’s disease. PubMed PMC

Yan, Y. et al. Gut microbiota and metabolites of alpha-synuclein transgenic monkey models with early stage of Parkinson’s disease. PubMed PMC

Tisch, U. et al. Detection of Alzheimer’s and Parkinson’s disease from exhaled breath using nanomaterial-based sensors. PubMed

Lau, H. C., Yu, J. B., Lee, H. W., Huh, J. S. & Lim, J. O. Investigation of Exhaled Breath Samples from Patients with Alzheimer’s Disease Using Gas Chromatography-Mass Spectrometry and an Exhaled Breath Sensor System. PubMed PMC

Bach, J. P. et al. Measuring Compounds in Exhaled Air to Detect Alzheimer’s Disease and Parkinson’s Disease. PubMed PMC

Compta, Y. & Revesz, T. Neuropathological and Biomarker Findings in Parkinson’s Disease and Alzheimer’s Disease: From Protein Aggregates to Synaptic Dysfunction. PubMed PMC

Kumar, A. & Sharma, C. Recent update of the various sources originating ghost peaks in gas chromatography: A review. PubMed

Nakhleh, M. K. et al. Distinguishing idiopathic Parkinson’s disease from other parkinsonian syndromes by breath test. PubMed

Tang, C. C. et al. Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis. PubMed PMC

Nakhleh, M. K. et al. Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules. PubMed PMC

Stott, S. et al. The Utility of Breath Analysis in the Diagnosis and Staging of Parkinson’s Disease. PubMed

Mitra, A. et al. The Human Skin Volatolome: A Systematic Review of Untargeted Mass Spectrometry Analysis. PubMed PMC

Morgan, J. Joy of super smeller: sebum clues for PD diagnostics. PubMed

Trivedi, D. K. et al. Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum. PubMed PMC

Sinclair, E. et al. Validating Differential Volatilome Profiles in Parkinson’s Disease. PubMed PMC

Fu, W. et al. Artificial Intelligent Olfactory System for the Diagnosis of Parkinson’s Disease. PubMed PMC

Tan, A. H. et al. Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi-Omics. PubMed

Ren, T. et al. Gut Microbiota Altered in Mild Cognitive Impairment Compared With Normal Cognition in Sporadic Parkinson’s Disease. PubMed PMC

Aho, V. T. E. et al. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease. PubMed PMC

Chen, S. J. et al. Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease. PubMed PMC

Siderowf, A. et al. Assessment of heterogeneity among participants in the Parkinson’s Progression Markers Initiative cohort using alpha-synuclein seed amplification: a cross-sectional study. PubMed PMC

Borghammer, P. & Van Den Berge, N. Brain-First versus Gut-First Parkinson’s Disease: A Hypothesis. PubMed PMC

Romano, S. et al. Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation. PubMed PMC

Sun, H. et al. Probiotics synergized with conventional regimen in managing Parkinson’s disease. PubMed PMC

Ouzzani, M., Hammady, H., Fedorowicz, Z. & Elmagarmid, A. Rayyan-a web and mobile app for systematic reviews. PubMed PMC

Page, M. J. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ PubMed PMC