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Sci Rep. 2017 Dec 7;7(1):17141. doi: 10.1038/s41598-017-17362-6.

A Pilot Characterization of the Human Chronobiome.

Author information

1
Department of Systems Pharmacology and Translational Therapeutics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. cskarke@pennmedicine.upenn.edu.
2
Department of Medicine, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. cskarke@pennmedicine.upenn.edu.
3
Institute for Translational Medicine and Therapeutics (ITMAT), at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. cskarke@pennmedicine.upenn.edu.
4
Department of Systems Pharmacology and Translational Therapeutics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
5
Institute for Translational Medicine and Therapeutics (ITMAT), at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
6
Department of Microbiology, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
7
Division of Gastroenterology, Hepatology, and Nutrition, at Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
8
Department of Food Science and Experimental Nutrition, Food Research Center (FoRC), School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
9
Institute for Biomedical Informatics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
10
Department of Genetics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
11
Department of Systems Pharmacology and Translational Therapeutics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. garret@upenn.edu.
12
Department of Medicine, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. garret@upenn.edu.
13
Institute for Translational Medicine and Therapeutics (ITMAT), at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. garret@upenn.edu.

Abstract

Physiological function, disease expression and drug effects vary by time-of-day. Clock disruption in mice results in cardio-metabolic, immunological and neurological dysfunction; circadian misalignment using forced desynchrony increases cardiovascular risk factors in humans. Here we integrated data from remote sensors, physiological and multi-omics analyses to assess the feasibility of detecting time dependent signals - the chronobiome - despite the "noise" attributable to the behavioral differences of free-living human volunteers. The majority (62%) of sensor readouts showed time-specific variability including the expected variation in blood pressure, heart rate, and cortisol. While variance in the multi-omics is dominated by inter-individual differences, temporal patterns are evident in the metabolome (5.4% in plasma, 5.6% in saliva) and in several genera of the oral microbiome. This demonstrates, despite a small sample size and limited sampling, the feasibility of characterizing at scale the human chronobiome "in the wild". Such reference data at scale are a prerequisite to detect and mechanistically interpret discordant data derived from patients with temporal patterns of disease expression, to develop time-specific therapeutic strategies and to refine existing treatments.

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