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.

Details

Title
A Pilot Characterization of the Human Chronobiome
Author
Skarke, Carsten 1   VIAFID ORCID Logo  ; Lahens, Nicholas F 2 ; Rhoades, Seth D 3 ; Campbell, Amy 3 ; Bittinger, Kyle 4 ; Bailey, Aubrey 5   VIAFID ORCID Logo  ; Hoffmann, Christian 6   VIAFID ORCID Logo  ; Olson, Randal S 7 ; Chen, Lihong 3 ; Yang, Guangrui 3 ; Price, Thomas S 3 ; Moore, Jason H 8 ; Bushman, Frederic D 9   VIAFID ORCID Logo  ; Greene, Casey S 2   VIAFID ORCID Logo  ; Grant, Gregory R 10 ; Weljie, Aalim M 2 ; FitzGerald, Garret A 1 

 Department of Systems Pharmacology and Translational Therapeutics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Medicine, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Institute for Translational Medicine and Therapeutics (ITMAT), at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA 
 Department of Systems Pharmacology and Translational Therapeutics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Institute for Translational Medicine and Therapeutics (ITMAT), at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA 
 Department of Systems Pharmacology and Translational Therapeutics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA 
 Department of Microbiology, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Division of Gastroenterology, Hepatology, and Nutrition, at Children’s Hospital of Philadelphia, Philadelphia, PA, USA 
 Department of Microbiology, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA 
 Department of Microbiology, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Food Science and Experimental Nutrition, Food Research Center (FoRC), School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil 
 Institute for Biomedical Informatics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA 
 Institute for Biomedical Informatics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Institute for Translational Medicine and Therapeutics (ITMAT), at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA 
 Department of Microbiology, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Institute for Translational Medicine and Therapeutics (ITMAT), at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA 
10  Institute for Translational Medicine and Therapeutics (ITMAT), at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Genetics, at the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA 
Pages
1-12
Publication year
2017
Publication date
Dec 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1983424996
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.