title: Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking.
abstract: Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20-30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption.
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois; garth_r_swanson@rush.edu.
authors.forename: Garth R
authors.initials: GR
authors.lastname: Swanson
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois;
authors.forename: Annika
authors.initials: A
authors.lastname: Gorenz
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois;
authors.forename: Maliha
authors.initials: M
authors.lastname: Shaikh
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois;
authors.forename: Vishal
authors.initials: V
authors.lastname: Desai
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois;
authors.forename: Thomas
authors.initials: T
authors.lastname: Kaminsky
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois;
authors.forename: Jolice
authors.initials: J
authors.lastname: Van Den Berg
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois;
authors.forename: Terrence
authors.initials: T
authors.lastname: Murphy
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois;
authors.forename: Shohreh
authors.initials: S
authors.lastname: Raeisi
authors.affiliation: ommunity, Systems and Mental Health Nursing, Rush University, Chicago, Illinois;
authors.forename: Louis
authors.initials: L
authors.lastname: Fogg
authors.affiliation: Department of Neurobiology, Center for Sleep and Circadian Biology, Northwestern University, Evanston, Illinois; Northwestern University Feinberg School of Medicine, Chicago, Illinois;
authors.forename: Martha Hotz
authors.initials: MH
authors.lastname: Vitaterna
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois;
authors.forename: Christopher
authors.initials: C
authors.lastname: Forsyth
authors.affiliation: Department of Neurobiology, Center for Sleep and Circadian Biology, Northwestern University, Evanston, Illinois; Northwestern University Feinberg School of Medicine, Chicago, Illinois;
authors.forename: Fred
authors.initials: F
authors.lastname: Turek
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois; Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois; and.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Burgess
authors.affiliation: Department Digestive Diseases, Rush University Medical Center, Chicago, Illinois; Departments of Pharmacology; Molecular Biophysics & Physiology, Rush University Medical Center, Chicago, Illinois.
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002940:Circadian Rhythm; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008550:Melatonin / Q000097:blood; D008875:Middle Aged; D010539:Permeability; D010561:Personnel Staffing and Scheduling; D012890:Sleep; D020178:Sleep Disorders, Circadian Rhythm / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D013997:Time Factors; D014940:Work Schedule Tolerance; D055815:Young Adult
chemical_list: D015415:Biomarkers; D056925:Circadian Rhythm Signaling Peptides and Proteins; D018836:Inflammation Mediators; D008550:Melatonin
keywords: alcoholic liver disease; intestinal permeability; melatonin