VOC biomarkers

The measurement of the volatile organic compounds (VOCs) produced by the body's metabolic activity is a powerful approach to monitoring health and diagnosing disease

A real-time chemical snapshot of the body's metabolism

The pattern of VOC biomarkers produced by the body reflects metabolic processes taking place within a person’s cells and tissues, within their microbiome, and from their response to environmental exposures.

Volatile organic compounds (VOCs) are gaseous molecules that can be sampled quickly and non-invasively from breath, urine or other bodily fluids. Particular patterns of VOC biomarkers are characteristic of specific disease processes, because their production is linked directly to metabolic activity in the body. Changes in the concentrations of VOCs occur at the very earliest stages of disease; detecting these VOC biomarkers can therefore allow for disease diagnosis before other physical symptoms have become apparent. Early diagnosis is critical in the successful treatment of cancer, as well as infectious and inflammatory diseases. VOC-img-01By providing patient specific, metabolomic information about a disease's characteristics, VOC biomarker analysis enables a precision medicine approach in therapy stratification, i.e. linking the right patient to the right treatment. As an example, treatment for severe asthma can be radically improved if those patients are stratified to receive the correct medication that best controls their particular type of asthma.

How is biomarker detection becoming an important tool in precision medicine-based drug treatment regimes?

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Metabolomics for diagnosis

Over the past two decades, a great deal of research has focused on genomics. While this science has made significant advances, it has not yet delivered on its full potential to help us understand and cure diseases. Genes serve as the blueprint for an organism’s biological functions, but it is rare that a single mutation will result in disease. In most circumstances, a disease is the result of multiple genetic attributes interacting with environmental factors, diet and lifestyle choices, microbiome differences and metabolic responses. 

Metabolism refers to life-sustaining biochemical processes that occur within any living organism. All organisms strive for metabolic homeostasis and constantly produce a variety of small molecules known as “metabolites” to achieve this biological balance. The type and quantity of circulating metabolites are central to the function of all living systems: this biochemical composition is also known as the metabolome.

When an organism’s biological systems are altered by disease, genetic mutations, or environmental factors, the profile of metabolites produced by these systems also changes. This response makes metabolites excellent candidates for biomarkers for early detection of disease, differentiating related disease states, and monitoring toxicities and other drug interactions.

In the case of cancer, the growth of each tumour is driven by accumulating genetic changes in bodily cells. These changes are small and variable but have a large uniform downstream effects: cells escape the immune system and grow in an unchecked manner. These effects are therefore reflected by cellular metabolism at a much larger scale. As metabolites are the end-product of cellular activity they are actively excreted into the extracellular space. Furthermore, tumour effects such as immune system activation, weight loss and increased oxidative stress all contribute to changes in the bodies metabolic signature.


Biomarkers in breath and urine

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All metabolites diffuse into the lymph and bloodstream and are ultimately excreted via breath, urine, or other bodily fluids. These can be captured and analysed to ascertain the presence and concentration of VOC biomarkers. They also have the great advantage that their collection, particularly for breath, is minimally invasive.


VOC biomarkers in breath

Gas exchange between circulating blood and inhaled fresh air across membranes in your lungs keeps you alive. Alongside oxygen, carbon dioxide, and other gases, VOC biomarkers also pass from the circulatory system into air inside the lungs. These biomarkers then exit the body as part of exhaled breath.

It takes blood about one minute to flow around the entire body, so by sampling all the breath exhaled during this period it is possible to non-invasively observe VOC biomarkers generated by any part of the body touched by the circulatory system.

Breath is particularly valuable for diagnosing diseases that reside in the lungs or airways. For example, VOC biomarkers originating from pulmonary tissue are relevant for diseases like lung cancer and metabolites relating to infectious bacterial diseases like tuberculosis. Breath analysis is also sensitive to potentially important endogeneous VOCs, such as drug metabolites.

As part of the STRATA (Stratification of Asthma Treatment by Breath Analysis) project, Owlstone Medical’s disease breathalyzer technology is being used to stratify asthma patients by inflammatory subtype, matching patients to the correct treatment to both improve patient outcomes and save healthcare organizations money.

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VOC biomarkers in urine

The kidneys primary function is to filter waste products from the blood. This provides a pre-concentration of metabolites, making it an excellent matrix for the detection of disease VOC biomarkers. Like breath, it is also a minimally invasive method of sampling that is already very widely used in healthcare.

This approach is used in the detection of colorectal cancer biomarkers in the InTERCEPT project.

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