Mapping the Shift Worker's Microbiome

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.

Inclusion criteria

• Cohort 1: healthy un-medicated males (to limit gender-induced variability similar to our pilot study), shift-work schedule (>3 shifts per month outside 7am-6pm (9)) for the past ≥10 years, 40-59 years old (increased prevalence of the metabolic syndrome at ≥60 years of age (20));
• Cohort 2: day workers who work 7am-6pm for ≥10 years matched for line of work, age, gender, and BMI;
• Volunteers are capable of giving informed consent;
• 40-59 years of age;
• Own an android smartphone which installs the remote sensing applications (those with apple smartphones will not be recruited);
• Non-smoking;
• Male subjects
• The use of contraception will NOT be required for male participants.

Exclusion criteria

• Recent travel across more than two (2) time zones (within the past month);
• Planned travel across more than two (2) time zones during the planned study activities;
• Use of illicit drugs;
• High dose vitamins (Vitamin A, Vitamin C, Vitamin E, Beta Carotene, Folic Acid and Selenium), alcohol and any over-the counter NSAID in the (2) two weeks before the start of the 48 hour deep phenotyping;
• High fat foods and caffeine in the past 24 hours prior to the 48-hour deep chronotyping session;
• History of abdominal surgery;
• Known allergy or intolerance to Vancomycin, and/or Neomycin;
• Use of anticholinergics in the week prior to the 48-hour sessions;
• Use of laxatives or anti-diarrhea medications in the two weeks prior to the 48-hour sessions;
• Subjects, who have received an experimental drug, used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening;
• Subjects with any abnormal laboratory value or physical finding that according to the investigator may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety of a potential subject;