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The One that Gut Away – Measuring Microbial VOCs from Breath

Non-invasive tools that are effective for disease screening, diagnosis and monitoring remain an unmet need in many disease areas. This article discusses breath volatile organic compounds (VOCs) as non-invasive biomarkers, and how breath, importantly to faecal VOCs, has the potential to reflect gut microbial activities, making it highly favourable for clinical application. More importantly, the article highlights an important interaction between gut microbial-produced VOCs and drug action, and by taking this into consideration during drug development, the pharmaceutical industry could improve the efficacy and patient-targeting capabilities of new drugs.

Volatile organic compounds (VOCs) are a large group of carbon-based chemicals that are emitted from biological samples, such as faeces, urine and breath. They include molecules such as short-chain fatty acids (SCFAs) and alcohols, which are well-known products of the microbiome. VOCs produced in the body come from cellular metabolic activities, reflecting the physiological state, and have a high potential to serve as disease biomarkers. The collection of VOCs from all biological samples is non-invasive, however, the measurement of VOCs on the breath is preferable over other biological samples for several reasons including; ease of sampling and repeat sampling within a short time frame, samples taken in real-time reflecting metabolic activity at a precise time point, and reduced variability due to standardised sample collection.

Breath VOCs can originate from either within the body (endogenous VOCs) or from external sources including dietary and environmental exposures (exogenous VOCs). Changes to the levels of endogenous VOCs can be characteristic of specific disease processes as they are often products of metabolic activity in the body. However, many metabolites produced by the human body are not derived from human metabolism – they can also originate from microbes within the gut. VOCs produced by microbes in the gut have been studied far less despite these VOCs showing links to several disease areas including gastrointestinal diseases.1,2 Many of the gut microbial-produced VOCs come from the metabolism of dietary fibre. Dietary fibres, which cannot be metabolised by the human body, are fermented by gut microbes, the metabolism of which produces volatile SCFAs and alcohols. Other known volatile microbial metabolites include phenol, phenyl acetaldehyde and p-cresol, which are produced through aromatic amino acid catabolism. Many of these gut microbial-produced VOCs are beneficial to the body and may regulate both local and distant immune, neuronal and metabolic responses. Changes in the levels of these VOCs could therefore imply gut microbiota composition and/or diversity changes, as well as its associated diseases such as cancer, gastrointestinal disorders and cardiovascular disease.