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

Volatile organic compounds (VOCs) are gaseous molecules that can be sampled quickly and non-invasively from breath. They can originate either from within the body (endogenous VOCs) or from external sources such as diet, prescription drugs and environmental exposure (exogenous VOCs). With over 1,000 VOCs present in breath, they are a rich source of information regarding the overall state of health of individuals. In particular, since the production of endogenous VOCs is linked directly to metabolic activity in the body, particular patterns of these VOCs can be biomarkers characteristic of specific disease processes, while measuring the levels of exogenous VOCs in breath can be used to determine how drugs are being processed within the body, or to measure exposure to potentially harmful compounds in the environment, such as benzene. And if there are particular metabolic pathways we are interested in, we can use isotope-marked compounds where, for instance, a 12C atom is replaced by a heavier 13C one. We can then determine whether the molecule is being broken down by looking for decay products, such as CO2, containing the heavier isotope (i.e. 13CO2).


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Metabolomics vs Genomics

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. 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.

Metabolomics vs Genomics

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

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VOCs in Cancer and the Warburg Effect

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, tumor effects such as immune system activation, weight loss and increased oxidative stress all contribute to changes in the body’s metabolic signature.

One particularly notable metabolic change associated with cancer is the Warburg effect, with a hugely increased glycolysis rate in cancerous cells. This leads to significantly raised levels of metabolites such as lactate and fumarate, noticeably altering the VOC profile in breath.

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VOC biomarkers in Inflammatory Disease

VOC biomarkers are also of use across a range of inflammatory disease. In asthma, for example, various VOCs, such as dodecane, cyclohexane and 2-butanone, reflect airway inflammation, and can be used to differentiate between different asthma phenotypes. Patients with inflammatory bowel disease (IBD), meanwhile, have been found to have elevated levels of ester, indole and short-chain fatty acids, likely due to dysbiosis of microbiota. Changes of the VOC profile of this kind have allowed Owlstone’s FAIMS technology to be used to detect IBD, and to differentiate between patients suffering from Crohn’s disease and those suffering from ulcerative colitis.

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