title: Circadian variation of the human metabolome captured by real-time breath analysis.
abstract: Circadian clocks play a significant role in the correct timing of physiological metabolism, and clock disruption might lead to pathological changes of metabolism. One interesting method to assess the current state of metabolism is metabolomics. Metabolomics tries to capture the entirety of small molecules, i.e. the building blocks of metabolism, in a given matrix, such as blood, saliva or urine. Using mass spectrometric approaches we and others have shown that a significant portion of the human metabolome in saliva and blood exhibits circadian modulation; independent of food intake or sleep/wake rhythms. Recent advances in mass spectrometry techniques have introduced completely non-invasive breathprinting; a method to instantaneously assess small metabolites in human breath. In this proof-of-principle study, we extend these findings about the impact of circadian clocks on metabolomics to exhaled breath. As previously established, our method allows for real-time analysis of a rich matrix during frequent non-invasive sampling. We sampled the breath of three healthy, non-smoking human volunteers in hourly intervals for 24 hours during total sleep deprivation, and found 111 features in the breath of all individuals, 36-49% of which showed significant circadian variation in at least one individual. Our data suggest that real-time mass spectrometric "breathprinting" has high potential to become a useful tool to understand circadian metabolism, and develop new biomarkers to easily and in real-time assess circadian clock phase and function in experimental and clinical settings.
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez-Lozano Sinues
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
authors.forename: Leila
authors.initials: L
authors.lastname: Tarokh
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Pulmonary Division, University Hospital Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Kohler
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Brown
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Renato
authors.initials: R
authors.lastname: Zenobi
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Dallmann
mesh_terms: D000328:Adult; D000388:Air / Q000032:analysis; D001944:Breath Tests; D057906:Circadian Clocks / Q000502:physiology*; D045853:Exhalation; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D012892:Sleep Deprivation / Q000378:metabolism