General molecules in cyan background

VOC Biomarkers

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

A Whole-body Metabolic Snapshot in Real-time

Volatile organic compounds (VOCs) are gaseous molecules that can be sampled quickly and non-invasively from breath with Breath Biopsy®. They can originate either from within the body (endogenous VOCs) or from external sources such as diet, prescription drugs and environmental exposure (exogenous VOCs).

Studies have identified over 1,000 VOCs that can be found on breath, alongside respiratory droplets they provide a rich source of information regarding overall health and have great potential as indicators of disease onset and progression.

Breath Analysis with Breath Biopsy

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Breath VOC Biomarkers Reflect the Patient Phenotype

Endogenous VOCs are products of metabolic activity in the body and changes to these VOCs can be characteristic of specific disease processes. Exogenous VOCs in breath can also be used to assess drug metabolism, or to measure exposure to potentially harmful compounds in the environment, such as benzene. Most recently we have developed exogenous VOC (EVOC®) Probes that can be administered in conjunction with a breath test to assess the activity of target metabolic pathways.

Lipid peroxidation and oxidative stress as sources of breath biomarkers

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Origins of VOCs

Endogenous volatile organic compounds are produced throughout the body and are picked up and distributed in the bloodstream. From the blood they exchange into air in the lungs and are then exhaled along with respiratory droplets and atmospheric gases. Exhaled VOCs provide a source of useful biomarkers with clear associations to the body's metabolism.

Breath Biopsy enables non-invasive collection and analysis of VOC biomarkers from breath. It takes roughly 1 minute for blood to flow around the entire circulatory system. By sampling breath for a minute or longer, even very low levels of VOC biomarkers from all parts of the body can be pre-concentrated, detected and identified. It’s easy to increase sensitivity to aid in detecting subtle changes during the very early stages of disease simply by extending sample collection time.

Advantages of Breath Sampling

Whole Body Blood Sampling

  • Your lungs are very effective at exchanging chemicals with your blood, including volatile metabolites and biomarkers that are generated even in the earliest stages of disease.
  • It takes ~1 minute for your blood volume to circle around your body once.
  • By continuosuly preconcentrating exhaled chemicals we can sample and analyze the entire circulating blood volume.
  • This is completely non-invasive and pain free.

Exogenous volatile organic compounds have a broader range of origins and have largely been overlooked as environmental contaminants in biological samples. More recently however, exogenous VOCs have become of increasing interest as many of them interact with biological systems and can also provide valuable information relevant to health and disease. For example, exogenous VOCs produced from the gut microbiome can be key health indicators.

We have further harnessed the power of exogenous VOCs as EVOC Probes. Many exogenous VOCs are processed within the body by core metabolic pathways, which are also often involved in drug metabolism. By administering EVOC Probes, we can assess the activity of these pathways, which may be relevant in treatment selection and precision medicine.

  

EVOC Probes

EVOC Probes

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Metabolomics vs Genomics

The genome is a powerful tool for understanding human biology, but it doesn’t contain the information needed for effective early disease detection and precision medicine. Metabolomics, the quantitative study of all the small molecules involved in metabolic pathways in the body, provides a much more complete picture.

Genes serve as the blueprint for an organism’s biological functions, but many diseases do not alter genetics and even in those that do genes rarely tell the whole story. 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.

Genomics can be used to predict your personal risk of developing an illness at some point in your life, while metabolomics can tell you if you have that disease now and how advanced it is. What’s more, detecting changes in the metabolome can be used to predict exacerbations, monitor response to treatment and detect adverse reactions or toxicities.

Breath Biopsy provides the means to non-invasively sample VOCs produced by the metabolome with relevance to a wide range of diseases, including respiratory diseases, liver diseases and cancers. The applications of Breath Biopsy span early detection, precision medicine and environmental research with specific utility in treatment monitoring and adverse reaction prediction during drug development.

Applications of Breath Biopsy

Towards standardization: Breath Biopsy® OMNI Assay for enhanced biomarker discovery

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VOCs and Disease Biology

Research is ongoing to establish clearer connections between specific VOCs and the biological processes involved in their production (find out more in our guest blog by Dr Rianne Fijten of Maastricht University). Below are just a few illustrations of the association between VOCs in major diseases.

 

Cancer and the Warburg Effect

It is increasingly clear that metabolism in cancer cells vastly differs from that of healthy cells. Metabolic changes can be some of the earliest detectable changes in cancer and become more pronounced as the disease develops. The resulting changes to exhaled VOCs are also added to by changes resulting from responses by the immune system. Cancer is notable for its rapid growth driven largely by energy generated by drastically increased glycolytic flux, known as the Warburg effect. Elevated glycolysis leads to increases in lactate and fumarate metabolites resulting in altered VOC abundances in exhaled breath.

Cancer and the Warburg Effect

Click the button to read more about Breath Biopsy for early cancer detection in articles written by Dr Balkees Abderrahman, MD Anderson researcher and one of Forbes 30 Under 30 for Science.

Breath Biopsy for Early Cancer Detection

 

VOC Biomarkers in Inflammatory Disease

The metabolic changes caused by inflammation are relevant in a range of diseases and can be detected through VOCs on breath. For example, VOCs such as undecane, 3-methylhexane and 1-pentadecene, reflect airway inflammation in respiratory diseases. Similarly, patients with inflammatory bowel disease (IBD) show elevated levels of ester, indole and short-chain fatty acids. As such VOC profiles, detected using Owlstone Medical technologies, have been used to detect IBD and to differentiate the two main forms, Crohn’s disease and those suffering from ulcerative colitis.

VOC biomarkers in Inflammatory Disease

Oxidative Stress and Lipid Peroxidation As a Source of VOCs

An EVOC Probe for Fatty Liver Disease

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Results that indicate that limonene could be used to discriminate cirrhosis.
Fatty liver disease is a growing issue worldwide and is a prime target for investigation using VOCs on breath. Several studies, most recently one using Breath Biopsy, show that an increase in the exogenous VOC limonene is a strong indicator of cirrhosis. The level of limonene on breath even falls when cirrhosis patients receive a liver transplant. Limonene is commonly found in foods and drink, particularly orange juice, so is an ideal EVOC Probe for assessing liver function.

We are currently investigating whether limonene can be used to detect early stage fatty liver diseases such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

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