The Circadian Clock Mutation Promotes Intestinal Dysbiosis.

ABSTRACT: 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.Male Clock(?19) -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.The fecal microbial community of Clock-mutant mice had lower taxonomic diversity, relative to wild-type mice, and the Clock(?19) 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.Our data support a model by which circadian rhythm disruption by the Clock(?19) mutation perturbs normal intestinal microbial communities, and this trend was exacerbated in the context of a secondary dietary intestinal stressor.

SUBMITTER: Voigt RM 

PROVIDER: S-EPMC4977829 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature