Gut microbiota from coronary artery disease patients contributes to vascular dysfunction in mice by regulating bile acid
- PDF / 2,721,831 Bytes
- 18 Pages / 595.276 x 790.866 pts Page_size
- 15 Downloads / 156 Views
Journal of Translational Medicine Open Access
RESEARCH
Gut microbiota from coronary artery disease patients contributes to vascular dysfunction in mice by regulating bile acid metabolism and immune activation Honghong Liu1†, Ran Tian1†, Hui Wang1, Siqin Feng1, Hanyu Li1, Ying Xiao1, Xiaodong Luan1, Zhiyu Zhang1, Na Shi2, Haitao Niu3* and Shuyang Zhang1*
Abstract Background: The gut microbiota was shown to play a crucial role in the development of vascular dysfunction, and the bacterial composition differed between healthy controls and coronary artery disease patients. The goal of this study was to investigate how the gut microbiota affects host metabolic homeostasis at the organism scale. Methods: We colonized germ-free C57BL/6 J mice with faeces from healthy control donors (Con) and coronary artery disease (CAD) patients and fed both groups a high fat diet for 12 weeks. We monitored cholesterol and vascular function in the transplanted mice. We analysed bile acids profiles and gut microbiota composition. Transcriptome sequencing and flow cytometry were performed to evaluate inflammatory and immune response. Results: CAD mice showed increased reactive oxygen species generation and intensive arterial stiffness. Microbiota profiles in recipient mice clustered according to the microbiota structure of the human donors. Clostridium symbiosum and Eggerthella colonization from CAD patients modulated the secondary bile acids pool, leading to an increase in lithocholic acid and keto-derivatives. Subsequently, bile acids imbalance in the CAD mice inhibited hepatic bile acids synthesis and resulted in elevated circulatory cholesterol. Moreover, the faecal microbiota from the CAD patients caused a significant induction of abnormal immune responses at both the transcriptome level and through the enhanced secretion of cytokines. In addition, microbes belonging to CAD promoted intestinal inflammation by contributing to lamina propria Th17/Treg imbalance and worsened gut barrier permeability. Conclusions: In summary, our findings elucidated that the gut microbiota impacts cholesterol homeostasis by modulating bile acids. In addition, the CAD-associated bacterial community was shown to function as an important regulator of systemic inflammation and to influence arterial stiffness. Keywords: Gut microbiota, Faecal microbiota transplantation, Bile acids, Intestinal immunity, Vascular dysfunction
*Correspondence: [email protected]; [email protected] † Honghong Liu and Ran Tian contributed equally to this work 1 Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China 3 School of Medicine, Jinan University, Guangzhou 510632, China Full list of author information is available at the end of the article
Background Mounting evidence indicates a strong link between intestinal dysbiosis and the development of cardiovascular diseases (CVD). A wide variety of bacterial derivative metabolites have
Data Loading...
