A multi-omics study of the association between insomnia with objective short sleep duration phenotype and high blood pressure

Abstract Study Objectives Insomnia with objective short sleep duration is associated with increased hypertension risk. We aimed to explore the mechanism underlying the association between objective short sleep duration and hypertension in patients with chronic insomnia disorder (CID) by multi-omics. Methods CID was defined according to International Classification of Sleep Disorders-3, and objective short sleep was based on the median value of total sleep time of the overall subjects during an overnight polysomnography. We used the mean values of measured nighttime and morning systolic (SBP) and diastolic blood pressure (DBP) for analysis. Serum metabolomics and fecal 16S rDNA amplicon sequencing were used to explore characteristic metabolites and analyze gut microbiota distribution, respectively. Results One hundred three patients with CID and 70 normal sleepers were included. We found 52 objective short sleep duration insomnia phenotype (ISSD)-related serum metabolites. Among the 52 ISSD-related serum metabolites, indoxyl sulfate was positively correlated with BP after adjusting for confounding factors (SBP: β=0.250, p=0.028; DBP: β=0.256, p=0.030) in ISSD. In addition, the level of serum indoxyl sulfate was significantly correlated with the genera Prevotella 9 (r=0.378, p=0.027), CAG-56 (r=-0.359, p=0.037), Ruminiclostridium 9 (r=-0.340, p=0.049) and Ruminococcus 2 (r=-0.356, p=0.039) in ISSD. Conclusions Our study suggests that the ISSD phenotype is associated with significant changes in serum metabolic profile, including high levels of indoxyl sulfate. The latter molecule correlates both with BP and gut microbiota in patients with the ISSD phenotype, suggesting that indoxyl sulfate may be the molecular path resulting in increased hypertension risk in this phenotype.