Qiuxia Liu1, Yuchuan Li1, Xue Song1, Jing Wang2, Zebao He3, Jiansheng Zhu4, Huazhong Chen4, Jing Yuan5, Xue Zhang1, Haiyin Jiang1, Sheng Zhang6, Bing Ruan7. 1. The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, College of Medicine, Zhejiang University, Hangzhou, China. 2. The First Affiliated Hospital, Department of Cardiology, College of Medicine, Zhejiang University, Hangzhou, China. 3. Department of Infectious Diseases, Taizhou Enze Medical Center (Group) Enze Hospital, Taizhou, China. 4. Department of Infectious Diseases, Affiliated Taizhou Hospital of Wenzhou Medical University, Linhai, China. 5. The Third People's Hospital of Shenzhen, Shenzhen, China. 6. Institute of Biotechnology, Cornell University, Ithaca, NY, United States. 7. The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address: ruanbing@zju.edu.cn.
Abstract
BACKGROUND: Several studies have suggested a role for the gut microbiome and cytokines in atherosclerosis development, but combined analyses of the changes of the gut microbiota and cytokines have not been explored previously. METHODS: We treated ApoE-/- and wild-type mice with a high-fat diet for 12 weeks. The gut microbiome and cytokine composition were analyzed using 16S ribosomal DNA sequencing and RayBio Quantibody Arrays, respectively. GO and KEGG analysis were performed to rationalize the potential mechanisms involved in the process of atherosclerosis. RESULTS: Gut bacterial characteristics in ApoE-/- mice were clearly separated and 21 gut bacterial clades were detected by the LEfSe analysis showing significant differences during the development of atherosclerosis. The relative abundance of Verrucomicrobia, Bacteroidaceae, Bacteroides, and Akkermansia showed significant positive correlations with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, the relative abundance of Ruminococcaceae was positive with the level of HDL and the abundance of Rikenellaceae showed a negative relationship with the level of TG and LDL. Thirteen differentially expressed proteins were identified with P-value < 0.05. CXCL5, FGF2, and E-Selectin were significantly negatively associated with Akkermansia and Verrucomicrobia. Additionally, CXCL5 was significantly negatively correlated with Bacteroides and Bacteroidaceae. Three "cellular component" subcategories, 24 ″molecular function" subcategories, 752 ″biological process" subcategories and 29 statistically remarkable KEGG pathway categories were identified. CONCLUSIONS: Gut microbiota changes of the mice having atherosclerosis and their relationship with the inflammatory status could be one of the major etiological mechanisms underlying atherosclerosis.
BACKGROUND: Several studies have suggested a role for the gut microbiome and cytokines in atherosclerosis development, but combined analyses of the changes of the gut microbiota and cytokines have not been explored previously. METHODS: We treated ApoE-/- and wild-type mice with a high-fat diet for 12 weeks. The gut microbiome and cytokine composition were analyzed using 16S ribosomal DNA sequencing and RayBio Quantibody Arrays, respectively. GO and KEGG analysis were performed to rationalize the potential mechanisms involved in the process of atherosclerosis. RESULTS: Gut bacterial characteristics in ApoE-/- mice were clearly separated and 21 gut bacterial clades were detected by the LEfSe analysis showing significant differences during the development of atherosclerosis. The relative abundance of Verrucomicrobia, Bacteroidaceae, Bacteroides, and Akkermansia showed significant positive correlations with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, the relative abundance of Ruminococcaceae was positive with the level of HDL and the abundance of Rikenellaceae showed a negative relationship with the level of TG and LDL. Thirteen differentially expressed proteins were identified with P-value < 0.05. CXCL5, FGF2, and E-Selectin were significantly negatively associated with Akkermansia and Verrucomicrobia. Additionally, CXCL5 was significantly negatively correlated with Bacteroides and Bacteroidaceae. Three "cellular component" subcategories, 24 ″molecular function" subcategories, 752 ″biological process" subcategories and 29 statistically remarkable KEGG pathway categories were identified. CONCLUSIONS: Gut microbiota changes of the mice having atherosclerosis and their relationship with the inflammatory status could be one of the major etiological mechanisms underlying atherosclerosis.