Volatile Clues: Rethinking Parkinson’s Diagnosis Through Breath, Skin, and Stool

 

Parkinson’s disease (PD), a progressively debilitating neurological disorder, continues to challenge early diagnosis and effective monitoring. A new frontier is emerging from an unlikely source: our bodily odors. Volatile organic compounds (VOCs)—tiny molecules released in breath, skin, and stool—are now being studied as potential non-invasive biomarkers for PD, holding promise for earlier intervention and more personalized care. In this landmark review, Ilaria Belluomo and colleagues systematically analyze the state of VOC research in PD, highlighting both its scientific promise and the practical hurdles ahead.

The Science of Scent: How VOCs May Signal Disease

The human body emits hundreds of VOCs—metabolic by-products whose patterns can shift with disease. In PD, these changes may stem from gut microbiota imbalances, oxidative stress, or neurodegenerative processes. The review explores how researchers are detecting and interpreting these VOCs across multiple biological matrices:

  • Breath: Studies show altered profiles in PD patients, with compounds like pentane, nonanal, and acetone appearing more frequently. Sensor arrays coupled with gas chromatography-mass spectrometry (GC-MS) show promising classification accuracy—raising hopes for scalable, non-invasive diagnostic tests.
  • Skin: Spurred by the story of Joy Milne—a “super smeller” who sensed PD in her husband’s odor years before diagnosis—researchers have identified altered sebum composition in PD patients. Key compounds include hippuric acid and octadecanal, although external contamination and identification challenges persist.
  • Stool: VOCs such as short-chain fatty acids (SCFAs), which are produced by gut microbes, have shown promise in both animal and human studies. Disruptions in these molecules may reflect early pathophysiological changes and influence neuroinflammation.

Preclinical Insights: Animal Models Reveal Mechanistic Clues

In PD animal models, changes in VOCs, particularly SCFAs and alkanes, correlate with neuroinflammation, microbiome dysbiosis, and oxidative stress. Fecal microbiota transplantation and dietary interventions have been shown to restore VOC profiles and mitigate PD symptoms in mice—underscoring the gut-brain axis as a therapeutic and diagnostic target.

Technological Landscape: From GC-MS to Nanosenors

GC-MS remains the gold standard for VOC identification, prized for its sensitivity and precision. Yet, it is time-consuming and technically demanding. Emerging tools like ion mobility spectrometry and nanomaterial-based sensors offer rapid, real-time results, though they currently lack compound specificity. The future lies in combining these methods for robust VOC profiling and real-world application.

Microbiome Metabolism: A Volatile Partnership

The gut microbiota’s influence on VOC production is a focal point of this review. Disrupted microbial communities in PD patients—especially loss of SCFA-producing taxa—are linked to altered VOC levels and symptom severity. Metagenomic and multi-omics studies point to changes in metabolic pathways involving bile acid degradation, amino acid biosynthesis, and neuroinflammatory signaling.

Barriers and Breakthroughs: What Still Needs to Happen

Despite exciting early results, the field faces substantial obstacles:

  • Lack of standardization in sample collection and analysis.
  • Small, heterogeneous patient cohorts.
  • Inconsistent VOC findings and poor reproducibility.
  • Unclear causal links between specific compounds and PD mechanisms.

The authors stress the need for large-scale, multicenter trials, better matching of control groups, and validation of biomarkers in early-stage, drug-naïve patients.

Conclusion: Toward a Smarter, Smoother Diagnosis

Volatile organic compounds represent a compelling and underexplored dimension in the diagnosis and monitoring of Parkinson’s disease. While challenges in standardization, validation, and mechanistic understanding remain, this review paints a cautiously optimistic future. Breath, skin, and stool—once ignored biological signals—may soon become powerful tools in personalized neurology.

As the scent of science sharpens, so too does our capacity to detect disease where we once smelled nothing at all.

The Digital Olfaction Revolution 

Looking ahead, the role of digital olfaction may become transformative in this space. Devices capable of detecting, digitizing, and wirelessly transmitting VOC profiles in real-time could revolutionize disease monitoring—bringing diagnostics from specialized labs to the patient’s bedside or even home. This convergence of biology and technology may define the next chapter in Parkinson’s care.

Reference: Belluomo, I., Tarazi, M., Lao-Kaim, N.P. et al. Detection of Volatile Organic Compounds as an emerging strategy for Parkinson’s disease diagnosis and monitoring. npj Parkinsons Dis. 11, 161 (2025). https://doi.org/10.1038/s41531-025-00993-2