The Circadian Clock Mutation Promotes Intestinal Dysbiosis.

Autor: Voigt RM; Department of Internal Medicine , Division of Gastroenterology, Rush University Medical Center, Chicago, Illinois., Summa KC; Center for Sleep and Circadian Biology , Department of Neurobiology, Northwestern University, Evanston, Illinois., Forsyth CB; Department of Internal Medicine , Division of Gastroenterology, Rush University Medical Center, Chicago, Illinois.; Department of Biochemistry , Rush University Medical Center, Chicago, Illinois., Green SJ; DNA Services Facility , Research Resources Center, University of Illinois at Chicago, Chicago, Illinois.; Department of Biological Sciences , University of Illinois at Chicago, Chicago, Illinois., Engen P; Department of Internal Medicine , Division of Gastroenterology, Rush University Medical Center, Chicago, Illinois., Naqib A; DNA Services Facility , Research Resources Center, University of Illinois at Chicago, Chicago, Illinois., Vitaterna MH; Center for Sleep and Circadian Biology , Department of Neurobiology, Northwestern University, Evanston, Illinois., Turek FW; Center for Sleep and Circadian Biology , Department of Neurobiology, Northwestern University, Evanston, Illinois., Keshavarzian A; Department of Internal Medicine , Division of Gastroenterology, Rush University Medical Center, Chicago, Illinois.; Department of Pharmacology , Rush University Medical Center, Chicago, Illinois.; Division of Pharmacology , Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
Jazyk: angličtina
Zdroj: Alcoholism, clinical and experimental research [Alcohol Clin Exp Res] 2016 Feb; Vol. 40 (2), pp. 335-47.
DOI: 10.1111/acer.12943
Abstrakt: Background: Circadian rhythm disruption is a prevalent feature of modern day society that is associated with an increase in pro-inflammatory diseases, and there is a clear need for a better understanding of the mechanism(s) underlying this phenomenon. We have previously demonstrated that both environmental and genetic circadian rhythm disruption causes intestinal hyperpermeability and exacerbates alcohol-induced intestinal hyperpermeability and liver pathology. The intestinal microbiota can influence intestinal barrier integrity and impact immune system function; thus, in this study, we sought to determine whether genetic alteration of the core circadian clock gene, Clock, altered the intestinal microbiota community.
Methods: Male Clock(Δ19) -mutant mice (mice homozygous for a dominant-negative-mutant allele) or littermate wild-type mice were fed 1 of 3 experimental diets: (i) a standard chow diet, (ii) an alcohol-containing diet, or (iii) an alcohol-control diet in which the alcohol calories were replaced with dextrose. Stool microbiota was assessed with 16S ribosomal RNA gene amplicon sequencing.
Results: The fecal microbial community of Clock-mutant mice had lower taxonomic diversity, relative to wild-type mice, and the Clock(Δ19) mutation was associated with intestinal dysbiosis when mice were fed either the alcohol-containing or the control diet. We found that alcohol consumption significantly altered the intestinal microbiota in both wild-type and Clock-mutant mice.
Conclusions: Our data support a model by which circadian rhythm disruption by the Clock(Δ19) mutation perturbs normal intestinal microbial communities, and this trend was exacerbated in the context of a secondary dietary intestinal stressor.
(Copyright © 2016 by the Research Society on Alcoholism.)
Databáze: MEDLINE
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