Volatile Organic Compounds: The next frontier in non-invasive detection of microbial infection

Volatile Organic Compounds (VOCs) are chemical compounds containing carbon that have a high enough vapour pressure under normal conditions to significantly vaporise and enter the atmosphere. VOCs are continuously being produced by our body’s metabolism and released into the air predominantly via our skin, breath, faeces and urine. VOCs can instantaneously reflect physiological and pathological biochemical processes occurring in the body at the time of measurement. 

This identification of VOCs opens a non-invasive yet objective and measurable window into normal and abnormal metabolic pathways, and also illustrates how these pathways are altered and even respond to therapy in disease processes. Any change in the metabolism equilibrium can cause an alteration of human VOC.

Microorganisms release volatile organic compounds (VOCs) and the ability to identify these in infected cutaneous wounds could lead to efficient non-invasive diagnosis. Therefore, the use of VOCs for the identification of infection in human skin is a promising technological approach which should be receiving growing interest.

Diagnostic procedures using VOCs are non-invasive and thus are an attractive alternative for patients compared to current invasive laboratory tests performed in hospitals which additionally take significant time and cannot provide instant point of care testing. Current cutaneous wound infection diagnosis mainly involves clinical judgement in combination with microbiological analyses of wound swabs. 

Modern analytical technology fortunately provides a reliable  platform to obtain detailed quantitative analysis of VOCs. Gas chromatography-mass spectrometry is the preferred universal analytic method for studying VOC profiles due to its sensitivity and specificity. Gas chromatography works by capturing electrons as compounds which enter the current. The process of capturing the electrons decreases the current which is reproduced as spikes in the form of a chromatogram. 

The epidermis of the skin continuously sheds thousands of cells into the environment, which are replaced by differentiating cells from the layer below. These dead cells transport body secretions and importantly bacteria, which act on the dead cells and envelope them in a minute vapour cloud. A complex profile of VOCs emanates from human skin, which is altered by changes in the body's metabolic or hormonal state, the external environment, and the bacterial species colonising the skin surface (the microbiome). For a comprehensive review that can provide a detailed information on VOCs produced and emitted by bacterial species commonly associated with cutaneous wound infections; please see our review published in the journal Wound Repair & Regeneration https://www.ncbi.nlm.nih.gov/pubmed/28727229.

An early study from my group showcased a reproducible, robust, non-invasive methodology that was applicable in a clinical setting and could offer a new, hitherto unexplored, class of biochemical markers underpinning the metabolism of chronic wounds. https://www.ncbi.nlm.nih.gov/pubmed/20492633

Subsequent to this, we set out to establish the formation, development and maturation of common cutaneous wound pathogenic bacterial biofilms on human ex vivo incisional and excisional cutaneous wound models. We then presented for the first-time bacterial biofilm formation in human ex vivo cutaneous wound models and their specific VOC profiles. These models provide a vehicle for human skin-relevant biofilm studies and VOC detection has potential clinical translatability in efficient non-invasive diagnosis of wound infection. https://www.ncbi.nlm.nih.gov/pubmed/29930327

Following on from our previous in vitro, ex vivo and in patient VOC assessment, we then set out to measure VOC formation in vivo again but this time, in sequentially temporal acute cutaneous wounds created in human volunteers. Therefore, in this study, profiling skin microbiome and metabolome has now been combined in order to gain further insight into the acute wound healing processes. This study entitled ‘microbiome and metabolomic signature of phases of cutaneous healing identified by profiling sequential acute wounds of human skin’;  https://www.ncbi.nlm.nih.gov/pubmed/32106276. This exploratory study demonstrated the temporal and dynamic nature of acute wound metabolome and microbiome and presented a novel class of biomarkers which can correspond to wound healing, with further confirmatory studies now necessary.

What remains unknown is the relevance of this technology in better detection of not only bacterial but also fungal and viral infections, could this approach offer a quicker way of identifying specific metabolites: such as post corona viral infection and be the panacea for COVID-19 detection?