The Human Skin Volatolome: A Systematic Review of Untargeted Mass Spectrometry Analysis

Anuja Mitra, Sunyoung Choi, Piers R Boshier, Alexandra Razumovskaya-Hough, Ilaria Belluomo, Patrik Spanel, George B Hanna, Anuja Mitra, Sunyoung Choi, Piers R Boshier, Alexandra Razumovskaya-Hough, Ilaria Belluomo, Patrik Spanel, George B Hanna

Abstract

The analysis of volatile organic compounds (VOCs) can provide important clinical information (entirely non-invasively); however, the exact extent to which VOCs from human skin can be signatures of health and disease is unknown. This systematic review summarises the published literature concerning the methodology, application, and volatile profiles of skin VOC studies. An online literature search was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis, to identify human skin VOC studies using untargeted mass spectrometry (MS) methods. The principal outcome was chemically verified VOCs detected from the skin. Each VOC was cross-referenced using the CAS number against the Human Metabolome and KEGG databases to evaluate biological origins. A total of 29 studies identified 822 skin VOCs from 935 participants. Skin VOCs were commonly sampled from the hand (n = 9) or forearm (n = 7) using an absorbent patch (n = 15) with analysis by gas chromatography MS (n = 23). Twenty-two studies profiled the skin VOCs of healthy subjects, demonstrating a volatolome consisting of aldehydes (18%), carboxylic acids (12%), alkanes (12%), fatty alcohols (9%), ketones (7%), benzenes and derivatives (6%), alkenes (2%), and menthane monoterpenoids (2%). Of the VOCs identified, 13% had putative endogenous origins, 46% had tentative exogenous origins, and 40% were metabolites from mixed metabolic pathways. This review has comprehensively profiled the human skin volatolome, demonstrating the presence of a distinct VOC signature of healthy skin, which can be used as a reference for future researchers seeking to unlock the clinical potential of skin volatolomics. As significant proportions of identified VOCs have putative exogenous origins, strategies to minimise their presence through methodological refinements and identifying confounding compounds are discussed.

Keywords: exogenous compounds; healthy human volatolome; mass spectrometry; skin; translational science; volatile organic compounds.

Conflict of interest statement

The authors declare no conflict of interest. G.B.H is a founder of a cancer diagnostics company. I.B, P.R.B and G.B.H are named on patents related to volatile biomarkers.

Figures

Figure 1
Figure 1
PRISMA flow chart of literature.
Figure 2
Figure 2
The composition of the human skin volatolome in health and disease. (a) The composition of the skin volatolome from the top eight chemical classes from (i) healthy skin, (ii) infected skin, (iii) participants with melanoma, and (iv) patients with mixed visceral adenocarcinoma. (b) Percentage change in the skin VOC profile normalised to the healthy skin profile in a range of disease states.
Figure 3
Figure 3
The putative biological origins of skin volatile organic compounds emitted from human skin. The putative biological origins of the compounds representing the healthy human skin volatolome, grouped into endogenous, exogenous, and mixed origins. The most common compounds in each category are included; n represents the number of papers each compound was identified in.

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