Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats

Author:

Maki Katherine A.12,Burke Larisa A.3,Calik Michael W.1,Watanabe-Chailland Miki4,Sweeney Dagmar5,Romick-Rosendale Lindsey E.4,Green Stefan J.5,Fink Anne M.1

Affiliation:

1. Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, Illinois

2. Nursing Department, Nursing Research and Translational Science, National Institutes of Health, Clinical Center, Bethesda, Maryland

3. Office of Research Facilitation, College of Nursing, University of Illinois at Chicago, Chicago, Illinois

4. NMR-Based Metabolomics Core, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

5. Genome Research Core, Research Resources Center, University of Illinois at Chicago, Chicago, Illinois

Abstract

The gut microbiota, via the production of metabolites entering the circulation, plays a role in blood pressure regulation. Blood pressure is also affected by the characteristics of sleep. To date, no studies have examined relationships among the gut microbiota/metabolites, blood pressure, and sleep. We hypothesized that fragmented sleep is associated with elevated mean arterial pressure, an altered and dysbiotic gut microbial community, and changes in fecal metabolites. In our model system, rats were randomized to 8 h of sleep fragmentation during the rest phase (light phase) or were undisturbed (controls) for 28 consecutive days. Rats underwent sleep and blood pressure recordings, and fecal samples were analyzed during: baseline ( days −4 to −1), early sleep fragmentation ( days 0–3), midsleep fragmentation ( days 6–13), late sleep fragmentation ( days 20–27), and recovery/rest ( days 28–34). Less sleep per hour during the sleep fragmentation period was associated with increased mean arterial pressure. Analyses of gut microbial communities and metabolites revealed that putative short chain fatty acid-producing bacteria were differentially abundant between control and intervention animals during mid-/late sleep fragmentation and recovery. Midsleep fragmentation was also characterized by lower alpha diversity, lower Firmicutes:Bacteroidetes ratio, and higher Proteobacteria in intervention rats. Elevated putative succinate-producing bacteria and acetate-producing bacteria were associated with lower and higher mean arterial pressure, respectively, and untargeted metabolomics analysis demonstrates that certain fecal metabolites are significantly correlated with blood pressure. These data reveal associations between sleep fragmentation, mean arterial pressure, and the gut microbiome/fecal metabolome and provide insight to links between disrupted sleep and cardiovascular pathology.

Funder

Office of Extramural Research, National Institutes of Health

Publisher

American Physiological Society

Subject

Genetics,Physiology

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