Mapping the gut microecological multi-omics signatures to serum metabolome and their impact on cardiometabolic health in elderly adultsResearch in context
Chu-wen Ling,
Kui Deng,
Yingdi Yang,
Hong-rou Lin,
Chun-ying Liu,
Bang-yan Li,
Wei Hu,
Xinxiu Liang,
Hui Zhao,
Xin-yi Tang,
Ju-Sheng Zheng,
Yu-ming Chen
Affiliations
Chu-wen Ling
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China; Department of Clinical Nutrition, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
Kui Deng
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China; Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, Center for Infectious Disease Research, School of Medicine, Westlake University, Hangzhou, 310030, China
Yingdi Yang
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
Hong-rou Lin
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
Chun-ying Liu
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
Bang-yan Li
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
Wei Hu
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
Xinxiu Liang
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, Center for Infectious Disease Research, School of Medicine, Westlake University, Hangzhou, 310030, China
Hui Zhao
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, Center for Infectious Disease Research, School of Medicine, Westlake University, Hangzhou, 310030, China
Xin-yi Tang
Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China; Corresponding author. Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Ju-Sheng Zheng
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, Center for Infectious Disease Research, School of Medicine, Westlake University, Hangzhou, 310030, China; Corresponding author. School of Medicine, Westlake University, 600 Dunyu Rd, Hangzhou, 310030, China.
Yu-ming Chen
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China; Corresponding author. Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.
Summary: Background: Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health. Methods: This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics. Findings: Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%–10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%–49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%–95%) and 19% (95% CI: 11%–27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks. Interpretation: This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites. Funding: This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the ‘Pioneer' and ‘Leading goose' R&D Program of Zhejiang.
