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The investigators hypothesize that disruptions to the microbiome of shift-workers represent a hitherto unexamined factor contributing to disease risk. The investigators will therefore define time-of-day dependent fluctuations of the microbiome in night shift workers and matched daytime workers deeply phenotyped for behavioral, clinical, and metabolomic outputs using integrated remote sensing.
Though several epidemiological studies have demonstrated that working night shift schedules are a risk factor for developing metabolic and cardiovascular diseases, the mechanisms through which this is conferred is not yet understood. Shift-work schedules alter employee's patterns of activity, light exposure and dietary intake in a manner incongruent with the endogenous clock. This circadian clock ensures that our metabolic activity occurs at maximally beneficial times of the day, but is largely unable to adapt to rapidly shifting schedules or sustained night-work. In mice, the investigators' lab has previously shown that genes relevant to all aspects of the metabolic syndrome are subject to circadian oscillation and that the gut microbiome is also subject to control by the host molecular clock. Despite the large contribution of our microbiome to host metabolism, the microbiome has been scarcely studied in the shift-working population. The investigators hypothesize that disruptions to the microbiome of shift-workers represent a hitherto unexamined factor contributing to disease risk. The investigators will therefore define time-of-day dependent fluctuations of the microbiome in night shift workers and matched daytime workers deeply phenotyped for behavioral, clinical, and metabolomic outputs using integrated remote sensing. The investigators will assess core body temperature, sleep/activity cycles, cortisol and melatonin as outputs determined by the host clock, and postprandial glucose and insulin levels as well as nocturnal blood pressure dipping as risk-related outputs. Through antibiotic-induced suppression, The investigators will determine the microbiome's specific contribution to these outputs. This has major implications for refining shift-work schedules and exploring therapeutic strategies in this population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Shift workers receive a standardized meal with a glucose challenge test |
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| Cohort 2 | Experimental | Matched healthy controls receive a standardized meal with a glucose challenge test |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standardized meal with a glucose challenge test | Other | Postprandial glucose and insulin response |
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| Measure | Description | Time Frame |
|---|---|---|
| Area under the glucose over time curve | Area under the curve (AUC) will be calculated from serial, timed glucose measurements | 12 hour |
| Measure | Description | Time Frame |
|---|---|---|
| Time-of-day dependent fluctuations of the microbiome | Relative abundances assessed several times of day (morning, afternoon, evening, night with target times of 08:00, 14:00, 20:00, 02:00 +/- 1 hour) | 48 hours |
| Compound outcome derived from percent variance explained in communication (number of phone calls and text messages), mobility (miles traveled), light exposure, blood pressure, heart rate, heart rate variability, sleep/wake times, body core temperature |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carsten Skarke, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine | Philadelphia | Pennsylvania | 19104 | United States |
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To evaluate the linear relationships between every pairwise combination of variables in the integrated dataset, the R^2, or coefficient of determination, will be calculated for each pair using linear regression. A heat map of the proportion of variance in each variable (e.g. mobility, light exposure, systolic blood pressure) explained by each other variable will then be constructed to allow an integrative exploration of these data. Here, the advantage is that multiple assessments with different units of measure can be integrated to generate deep phenotypes. |
| 48 hours |
| Compound outcome derived from variance observed in multiomics outputs (metabolites, microbiota). | To explore factors contributing to the variance observed using principal components analysis | 48 hours |