Endogenous and microbial volatile organic compounds in cutaneous health and disease

Human skin is a region of high metabolic activity where a rich variety of biomarkers are secreted from the stratum corneum. The skin is a constant source of volatile organic compounds (VOCs) derived from skin glands and resident microbiota. Skin VOCs contain the footprints of cellular activities and thus offer unique insights into the intricate processes of cutaneous physiology. This review examines the growing body of research on skin VOC markers as they relate to skin physiology, whereby variations in skin-intrinsic and microbial metabolic processes give rise to unique volatile profiles. Emerging evidence for volatile biomarkers linked to skin perturbations and skin cancer are examined. Microbial-derived VOCs are also investigated as prospective diagnostic markers, and their potential to shape the composition of the local skin microbiota, and consequently cutaneous health, is considered. Finally, a brief outlook on emerging analytical challenges and opportunities for skin VOC-based research and diagnostics is presented.

💡 Research Summary

Human skin is a metabolically active organ that continuously releases a complex mixture of volatile organic compounds (VOCs) from both host cells and resident microorganisms. This review synthesizes current knowledge on skin‑derived VOCs, emphasizing their origins, analytical detection, physiological relevance, and potential as diagnostic biomarkers for skin disorders, including cancer.

The authors first distinguish two principal sources of skin VOCs. Endogenous VOCs arise from sebaceous and eccrine glands, as well as the stratum corneum, and include fatty acids, sterols, amino‑acid catabolites, and their oxidative products (e.g., 1‑octanol, hexanal, 2‑pentanone). These compounds reflect intrinsic processes such as lipid turnover, antioxidant defenses, and hormone metabolism. In parallel, the skin microbiome—dominated by Staphylococcus, Corynebacterium, Malassezia, and other taxa—produces microbial VOCs through pathways like amino‑acid deamination, fatty‑acid β‑oxidation, and sulfur metabolism, yielding alcohols, ketones, esters, and sulfides.

Analytical advances are central to the field. Gas chromatography–mass spectrometry (GC‑MS) remains the gold standard, with ionization techniques (photo‑ionization, chemical ionization) improving sensitivity and selectivity. Emerging platforms such as electronic noses, high‑resolution Fourier‑transform ion cyclotron resonance MS, and solid‑phase microextraction (SPME) enable rapid, non‑invasive profiling. Nevertheless, challenges persist: low VOC concentrations on the skin surface, environmental contamination, and the lack of standardized sampling protocols (e.g., patches, adsorbent tubes, direct swabs) limit reproducibility across studies.

Physiologically, a “baseline” VOC signature characterizes healthy skin. For instance, 6‑methyl‑heptane correlates with sebum oxidation, while 2‑pentanone is linked to keratin turnover. This baseline varies with age, sex, anatomical site, humidity, and temperature, underscoring the need for individualized reference ranges.

Disease‑related alterations are increasingly documented. In inflammatory conditions such as atopic dermatitis and psoriasis, the relative abundance of certain alcohols (1‑octanol, 2‑hexanol) rises, whereas lipid‑oxidation products (e.g., hexanone) decline. Infectious lesions display pathogen‑specific VOCs; Staphylococcus aureus, for example, emits 3‑methyl‑1‑butanol and methyl cyanide, which can serve as rapid infection markers. Notably, skin cancers—including melanoma and squamous‑cell carcinoma—exhibit distinct volatile profiles: elevated levels of 2‑butanone and hexanal, among others, reflect aberrant tumor metabolism and may enable non‑invasive early detection.

Beyond diagnostics, microbial VOCs may actively shape the skin ecosystem. Certain volatiles (e.g., isobutanol) possess antimicrobial properties that modulate community composition, while others can influence host immune responses. Understanding these interactions opens avenues for therapeutic manipulation, such as probiotic skin applications or VOC‑based modulators to restore a healthy microbiome.

The review concludes with a forward‑looking agenda: (1) develop universally accepted sampling and analytical standards; (2) integrate multi‑omics data (metabolomics, metagenomics, transcriptomics) to link VOC signatures with underlying biological pathways; (3) apply machine‑learning algorithms for pattern recognition and predictive modeling; and (4) translate laboratory findings into point‑of‑care devices capable of real‑time VOC monitoring. If these goals are achieved, skin VOCs could become cornerstone biomarkers for personalized dermatology, enabling early disease detection, monitoring of treatment response, and novel preventive strategies.