Cardiovascular and Gut Microbiome Responses to Sleep Disruption in Rats

The purpose of this dissertation was to determine how disrupted and fragmented sleep affect blood pressure and heart rate variability using a rat model. Epidemiological studies provide evidence that poor sleep leads to elevated cardiovascular disease risk. The study incorporated innovative microbiome and metabolomics methodologies to examine a possible role for the gut microbiome in the hypothesized link between poor sleep and the development of cardiovascular disease. Male Wistar Kyoto rats were randomized to undergo 8 hours of sleep disruption during the light-phase or to sleep undisturbed (controls) for 28 consecutive days. Rats underwent telemetric sleep and blood pressure recordings, and fecal samples were analyzed for 5 phases of the study: baseline (days -4 to -1), early sleep disruption (days 0–3), mid sleep disruption (days 6–13), late sleep disruption (days 20–27), and a recovery/rest period (days 28–34). The degree of sleep disruption predicted increases in systolic and diastolic blood pressure. In sleep disrupted rats, the normalized low frequency heart rate variability measure was decreased from baseline and the low frequency/high frequency ratio was increased from baseline during the recovery period, indicative of reduced parasympathetic stimulation to the heart. Short chain fatty acid- and succinate-producing bacteria were found to be differentially abundant during mid-/late- sleep disruption and recovery using 16S ribosomal ribonucleic acid gene amplicon sequencing and nuclear magnetic resonance-based metabolomics analysis. Elevated relative abundance of putative succinate-producing bacteria was associated with lower systolic and diastolic blood pressure levels and eight fecal metabolites were associated with blood pressure outcomes. The link between sleep disruption and elevated blood pressure may be exacerbated or mitigated by changes in short chain fatty acid- and other metabolite-producing bacteria in the gut.