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Induced volatolomics of pathologies

Abstract

Volatolomics allows us to elucidate cell metabolic processes in real time. In particular, a volatile organic compound (VOC) excreted from our bodies may be specific for a certain disease, such that measuring this VOC may afford a simple, fast, accessible and safe diagnostic approach. Yet, finding the optimal endogenous volatile marker specific to a pathology is non-trivial because of interlaboratory disparities in sample preparation and analysis, as well as high interindividual variability. These limit the sensitivity and specificity of volatolomics and its applications in biological and clinical fields but have motivated the development of induced volatolomics. This approach aims to overcome issues by measuring VOCs that result not from an endogenous metabolite but, rather, from the pathogen-specific or metabolic-specific enzymatic metabolism of an exogenous biological or chemical probe. In this Review, we introduce volatile-compound-based probes and discuss how they can be exploited to detect and discriminate pathogenic infections, to assess organ function and to diagnose and monitor cancers in real time. We focus on cases in which labelled probes have informed us about metabolic processes and consider the potential and drawbacks of the probes for clinical trials. Beyond diagnostics, VOC-based probes may also be effective tools to explore biological processes more generally.

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Fig. 1: Volatolomics and induced volatolomics.
Fig. 2: Sugar probes for assessing gastrointestinal disorders.
Fig. 3: A sugar probe for studying cancer metabolism in vivo and in vitro.
Fig. 4: Peptides for monitoring respiratory infections62.
Fig. 5: Labelled small molecules in the clinic.

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Acknowledgements

The authors thank the Ligue Contre le Cancer (Comité de la Vienne), the Cancéropôle Grand Sud-Ouest and the Région Nouvelle-Aquitaine for their financial support. They also thank Claude Geffroy for her precious help. Finally, the authors gratefully thank Sébastien Papot for his very wise advice.

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P.P. and F.D. researched data and literature for the article. All authors contributed to the discussion of content and writing. P.P. wrote the first version of the manuscript. All authors prepared the figures and reviewed and edited the manuscript before submission.

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Correspondence to Pauline Poinot.

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Glossary

Diabetes

A chronic condition associated with abnormally high levels of sugar (glucose) in the blood. Insulin produced by the pancreas lowers blood glucose. Absence or insufficient production of insulin, or an inability of the body to properly use insulin, causes diabetes.

Lactose intolerance

A disease found in approximately 70% of the adult world population that arises because of incomplete intestinal lactose absorption. Symptoms include colicky abdominal pain, flatulence and diarrhoea.

Small intestinal bacterial overgrowth

(SIBO). SIBO is characterized by an increased concentration of bacteria (>105 colony-forming units per ml) in the upper small intestine. In addition to the absolute number of organisms, the type of microbial flora seems to play an important role in the appearance of signs and symptoms. Although the majority of microbiota in the small bowel are Gram-positive organisms, the flora of patients with SIBO mainly comprises coliform bacteria and anaerobes. These microorganisms can ferment carbohydrates and may produce toxins that damage the intestinal mucous membrane, affecting its absorptive function.

Scintigraphy

A diagnostic technique in which a 2D picture of internal body tissue is produced through the detection of radiation emitted by a radioactive substance administered into the body.

Cytochrome P450

(CYP). A CYP is a monooxygenase enzyme with a conserved Phe-X(6−9)-Cys-X-Gly motif near its C terminus. The Cys thiolate binds a haem cofactor, the Fe site of which splits O2. One O atom is converted into H2O, while the other ends up on an organic substrate, with the oxidized product then being released from the enzymatic pocket. High interindividual variation in the activity profiles of these isoforms exist. If an individual is inherently deficient in a CYP or it is inhibited by another drug, toxicity may develop, particularly if drugs accumulate after multiple doses. Drug–drug interactions are a major cause of adverse drug reactions. CYPs themselves can have deleterious effects, converting some chemicals into toxic products that covalently bind enzymes, mitochondrial proteins, RNA, DNA and lipids.

Insulin resistance

This occurs when a normal or elevated insulin level produces an attenuated biological response. Classically, this refers to impaired sensitivity to insulin-mediated glucose disposal.

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Djago, F., Lange, J. & Poinot, P. Induced volatolomics of pathologies. Nat Rev Chem 5, 183–196 (2021). https://doi.org/10.1038/s41570-020-00248-z

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