Breath volatile organic compounds for the gut-fatty liver axis: Promise, peril, and path forward

Abstract

The worldwide interest in the gut microbiome and its impact on the upstream liver highlight a critical upside to breath research: it can uniquely measure otherwise unmeasurable biology. Bacteria make gases [volatile organic compounds (VOCs)] that are directly relevant to pathophysiology of the fatty liver and associated conditions, including obesity. Measurement of these VOCs and their metabolites in the exhaled breath, therefore, present an opportunity to safely and easily evaluate, on both a personal and a population level, some of our most pressing public health threats. This is an opportunity that must be pursued. To date, however, breath analysis remains a slowly evolving field which only occasionally impacts clinical research or patient care. One major obstacle to progress is that breath analysis is inherently and emphatically mutli-disciplinary: it connects engineering, chemistry, breath mechanics, biology and medicine. Unbalanced or incomplete teams may produce inconsistent and often unsatisfactory results. A second impediment is the lack of a well-known stepwise structure for the development of non-invasive diagnostics. As a result, the breath research landscape is replete with orphaned single-center pilot studies. Often, important hypotheses and key observations have not been pursued to maturation. This paper reviews the rationale and requirements for breath VOC research applied to the gut-fatty liver axis and offers some suggestions for future development.

Keywords: Breath, Volatile organic compounds, Fatty liver, Gut flora, Breath analysis

Core tip: The biology of the gut-liver axis has always been fascinating and exceedingly difficult to study. With the rapidly expanding interest in the gut microbiome, however, finding better measurement techniques to evaluate this biology has never been more relevant. Breath volatile organic compounds (VOCs) measurement presents the unmatched potential to address this critical unmet need. Breath measurement can be challenging, however, and requires coherent teams including engineers, breath chemists, and clinical researchers. It also requires long term vision and strategy. This paper describes the rationale for breath VOCs, critically reviews the history of breath VOC development, and offers suggestions for progress.