Sibo Zhu1,2,3, Kelin Xu2,4, Yanfeng Jiang1,2, Chengkai Zhu1, Chen Suo2,3, Mei Cui5, Yingzhe Wang5, Ziyu Yuan2, Jiangli Xue2, Jiucun Wang1,2, Tiejun Zhang3, Genming Zhao3, Weimin Ye6, Tingting Huang6, Ming Lu7, Weizhong Tian8, Li Jin1,2, Xingdong Chen1,2. 1. State Key Laboratory of Genetic Engineering and Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China. 2. Fudan University Taizhou Institute of Health Sciences, Taizhou, China. 3. Department of Epidemiology, School of Public Health, Fudan University, China. 4. Department of Biostatistics, School of Public Health, Fudan University; Key Laboratory of Public Health Safety, Fudan University, China. 5. Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China. 6. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 7. Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China. 8. Department of Medical Imaging, Taizhou People's Hospital Affiliated to Nantong University, Taizhou, Jiangsu, China.
Abstract
OBJECTIVES: An altered microbiota, which can be described quantitatively, has been identified as playing a pivotal role in host vascular physiology, and it may contribute to various diseases. The aim of this study was to better understand the role of the gut microbiota in vascular physiology in a subclinical elderly population, and to investigate how lifestyle affects the composition of host gut microbiota to further impact the pathogenesis of vascular diseases. METHODS: We performed a population-based faecal metagenomic study over 569 elderly asymptomatic subclinical individuals in rural China. An association network was built based on clinical measurements and detailed epidemiologic questionnaires, including blood chemistry, arterial stiffness, carotid ultrasonography, and metagenomic datasets. RESULTS: By analyzing the breadth, depth and impact of each node of the association network, we found carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were essential in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of eating fresh fruits and vegetables, and more exercise significantly reduced carotid atherosclerosis in terms of IMT, peak systolic velocity and end-diastolic velocity values through the mediation of Alistepes, Oligella and Prevotella. Gut microbes explained 16.5% of the mediation effect of lifestyle on the pathogenesis of carotid atherosclerosis. After adjustment, Faecalicatena [odds ratio (OR) = 0.12 ∼0.65] was shown to be protective against the formation of carotid atherosclerosis, independently, while Libanicoccus (OR = 1.46 ∼4.20 ) was associated with increased carotid arterial IMT. KEGG/KO Kyoto Encyclopedia of Genes and Genomes/ KEGG Orthology (KEGG/KO) analyses revealed a loss of anti-inflammation function in IMT subjects. CONCLUSION: Our study revealed a Chinese population-wide phenotype-metagenomic association network and a mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at potential therapeutic and preventive uses for microbiota in vascular diseases.
OBJECTIVES: An altered microbiota, which can be described quantitatively, has been identified as playing a pivotal role in host vascular physiology, and it may contribute to various diseases. The aim of this study was to better understand the role of the gut microbiota in vascular physiology in a subclinical elderly population, and to investigate how lifestyle affects the composition of host gut microbiota to further impact the pathogenesis of vascular diseases. METHODS: We performed a population-based faecal metagenomic study over 569 elderly asymptomatic subclinical individuals in rural China. An association network was built based on clinical measurements and detailed epidemiologic questionnaires, including blood chemistry, arterial stiffness, carotid ultrasonography, and metagenomic datasets. RESULTS: By analyzing the breadth, depth and impact of each node of the association network, we found carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were essential in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of eating fresh fruits and vegetables, and more exercise significantly reduced carotid atherosclerosis in terms of IMT, peak systolic velocity and end-diastolic velocity values through the mediation of Alistepes, Oligella and Prevotella. Gut microbes explained 16.5% of the mediation effect of lifestyle on the pathogenesis of carotid atherosclerosis. After adjustment, Faecalicatena [odds ratio (OR) = 0.12 ∼0.65] was shown to be protective against the formation of carotid atherosclerosis, independently, while Libanicoccus (OR = 1.46 ∼4.20 ) was associated with increased carotid arterial IMT. KEGG/KO Kyoto Encyclopedia of Genes and Genomes/ KEGG Orthology (KEGG/KO) analyses revealed a loss of anti-inflammation function in IMT subjects. CONCLUSION: Our study revealed a Chinese population-wide phenotype-metagenomic association network and a mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at potential therapeutic and preventive uses for microbiota in vascular diseases.
Authors: Zheng Wang; Brandilyn A Peters; Mykhaylo Usyk; Jiaqian Xing; David B Hanna; Tao Wang; Wendy S Post; Alan L Landay; Howard N Hodis; Kathleen Weber; Audrey French; Elizabeth T Golub; Jason Lazar; Deborah Gustafson; Seble Kassaye; Bradley Aouizerat; Sabina Haberlen; Carlos Malvestutto; Matthew Budoff; Steven M Wolinsky; Anjali Sharma; Kathryn Anastos; Clary B Clish; Robert C Kaplan; Robert D Burk; Qibin Qi Journal: Arterioscler Thromb Vasc Biol Date: 2022-06-09 Impact factor: 10.514