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Accelerating recovery from jet lag: prediction from a multi-oscillator model and its experimental confirmation in model animals.

ABSTRACT: The endogenous circadian clock drives oscillations that are completely synchronized with the environmental day-night rhythms with a period of approximately 24?hours. Temporal misalignment between one's internal circadian clock and the external solar time often occurs in shift workers and long-distance travelers; such misalignments are accompanied by sleep disturbances and gastrointestinal distress. Repeated exposure to jet lag and rotating shift work increases the risk of lifestyle-related diseases, such as cardiovascular complaints and metabolic insufficiencies. However, the mechanism behind the disruption of one's internal clock is not well understood. In this paper, we therefore present a new theoretical concept called "jet lag separatrix" to understand circadian clock disruption and slow recovery from jet lag based on the mathematical model describing the hierarchical structure of the circadian clock. To demonstrate the utility of our theoretical study, we applied it to predict that re-entrainment via a two-step jet lag in which a four-hour shift of the light-dark cycle is given in the span of two successive days requires fewer days than when given as a single eight-hour shift. We experimentally verified the feasibility of our theory in C57BL/6 strain mice, with results indicating that this pre-exposure of jet lag is indeed beneficial.

SUBMITTER: Kori H

PROVIDER: S-EPMC5405409 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Accelerating recovery from jet lag: prediction from a multi-oscillator model and its experimental confirmation in model animals.

Kori Hiroshi H Yamaguchi Yoshiaki Y Okamura Hitoshi H

Scientific reports 20170426

The endogenous circadian clock drives oscillations that are completely synchronized with the environmental day-night rhythms with a period of approximately 24 hours. Temporal misalignment between one's internal circadian clock and the external solar time often occurs in shift workers and long-distance travelers; such misalignments are accompanied by sleep disturbances and gastrointestinal distress. Repeated exposure to jet lag and rotating shift work increases the risk of lifestyle-related disea ...[more]

PMID: 28443630

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Project description:BackgroundEvidence suggests that circadian rhythm disorder is associated with a variety of gastrointestinal diseases, and the circadian rhythm plays a key role in maintaining the homeostasis of intestinal flora. The underlying mechanisms are still not completely identified. This study was aimed to explore whether jet lag-caused circadian disruption influences gut microbiome and its metabolites.MethodsMice were synchronized with 12-h light/dark cycles (control group) or subjected to daily 8-h advance of the light/dark cycle for every 3 days (jet-lagged group). Four months later, fecal samples and jejunal contents were collected and analyzed by 16S rRNA gene sequencing. In addition, fecal samples were subjected to metabolome analysis with ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).ResultsThe results of 16s rRNA sequencing showed that chronic jet lag led to decreased microbial abundance, richness, and diversity in both feces and jejunal contents. ANOSIM analysis revealed significant difference between control and jet-lagged groups. As the colonic microbiome, the abundance of Bacteroidetes phylum was significantly decreased and that of Actinobacteria phylum was increased in jet-lagged mice. Jet lag increased the ratio of Firmicutes to Bacteroidetes, an indicator for the imbalance of gut microbiota. Metabolome analysis of fecal samples showed that the levels of tryptophan and its derivatives were decreased in jet-lagged mice. In addition, fecal levels of secondary bile acids changed under jet lag conditions. Correlation analysis identified associations between tryptophan (and its derivatives) levels and colonic microbiota.ConclusionsThis study presents a comprehensive landscape of gut microbiota and its metabolites in mice subjected to chronic jet lag. The results suggest that circadian disruption may lead to changes in fecal and jejunal microbiota and fecal metabolites. Moreover, our results demonstrate a novel interplay between the gut microbiome and metabolome.

Dataset Information

Accelerating recovery from jet lag: prediction from a multi-oscillator model and its experimental confirmation in model animals.

Publications

Accelerating recovery from jet lag: prediction from a multi-oscillator model and its experimental confirmation in model animals.

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