Integration Analysis of Multi- Omics Data for Blood Pressure Studies in Early Postmenopausal Chinese Women

Background: Mounting evidence suggested associations between gut microbiota (GM), serum metabolites and blood pressure (BP). To date, the impact of GM and serum metabolites on BP variation was not well elucidated, particularly in postmenopausal women. Epidemiologic studies showed a higher prevalence of hypertension in postmenopausal women than in premenopausal women. Therefore, significant gut bacterial species and serum metabolites associated with BP in early postmenopausal women may serve as biomarkers for early diagnosis, prevention, intervention and treatment of hypertension in postmenopausal older women. Methods: In the present study, we carried out analyses on metagenomic, serum untargeted and targeted metabolomics and whole genome sequencing from 402 early postmenopausal Chinese women to search for early omics-biomarkers and gain novel insights into the potential mechanisms of BP regulation in postmenopausal women. Findings: We totally identified four gut bacterial species were significantly associated with both systolic BP and diastolic BP. Systematic integrative multi-omics analysis indicated that increased Bacteroides fragilis could elevate BP via decreased caproic acid, and phenylacetylglutamine mediated the causal relationships of both Bacteroides fragilis and Clostridium sp.CAG.226 on diastolic BP variation in early postmenopausal Chinese women. Interpretation: The application of systematic integrative multi-omics analysis discovered a list of candidate omics-biomarkers for future BP related biological experiments, which would be considered as potential biomarkers for early diagnosis, prevention, intervention and treatment of hypertension in older postmenopausal women, and detected the causal effects among GM, metabolic activity and BP variation. Funding Statement: Hong-Wen Deng was partially supported by grants from the National Institutes of Health [U19AG05537301, R01AR069055, P20GM109036, R01MH104680, R01AG061917, U54MD007595]. Hong-Mei Xiao was partially supported by the National Key R&D Program of China (2017YFC1001100 and 2016YFC1201805). Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. Ethics Approval Statement: All the participants had signed informed consent form before they were recruited, and this study was approved by the Third Affiliated Hospital of Southern Medical University (Guangzhou City, China) institutional review board.