The human skin volatolome: a systematic review of untargeted mass spectrometry analysis

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

Volatile organic compound emission from human skin

The analysis of volatile organic compounds (VOCs) emitted from the human body can provide personalised information about underlying metabolic pathophysiological processes entirely non- invasively. Despite the skin being the second largest contributor to the production of VOCs, it is an underexplored branch of the overall human volatolome and consequently the role of human skin to VOC production and the exact extent to which skin VOCs can be signatures of health and disease is unknown. This chapter explores the role of skin VOCs in the broader scientific and clinical context of the entire human volatolome. First, the literature landscape of the human volatolome and its clinical applications is described. The focus of this chapter then shifts to the human skin volatolome. Key methodological processes and challenges in skin VOC capture and analysis are considered. This is followed by a comprehensive summary and literature evaluation of research on skin VOCs in health and disease with a unique take on elucidating the biological origins of skin VOCs aiming to link the phenotype to the underlying disease process. Finally, the chapter concludes by discussing the current limitations of skin VOC research and concludes by highlighting future directions for research to be undertaken in this novel scientific field to strengthen the clinical translational value of skin VOCs