Gut microbiota from coronary artery disease patients contributes to vascular dysfunction in mice by regulating bile acid metabolism and immune activation.
Gut microbiota from coronary artery disease patients contributes to vascular dysfunction in mice by regulating bile acid metabolism and immune activation.
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冠状动脉疾病患者的肠道微生物群通过调节胆汁酸代谢和免疫激活导致小鼠血管功能障碍
DOI：
10.1186/s12967-020-02539-x
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发表时间：
2020-10-09
影响因子：
7.4
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Liu H;Tian R;Wang H;Feng S;Li H;Xiao Y;Luan X;Zhang Z;Shi N;Niu H;Zhang S
肠道微生物群在血管功能障碍的发展中起着至关重要的作用，健康对照组和冠状动脉疾病患者之间的细菌组成不同。本研究的目的是研究肠道微生物群如何影响生物体尺度上的宿主代谢稳态。我们用来自健康对照供体（Con）和冠状动脉疾病（CAD）患者的粪便定殖无菌C57 BL/6 J小鼠，并给两组喂食高脂肪饮食12周。我们监测了移植小鼠的胆固醇和血管功能。我们分析了胆汁酸谱和肠道微生物群组成。进行转录组测序和流式细胞术以评估炎症和免疫应答。CAD小鼠表现出活性氧生成增加和动脉僵硬。受体小鼠中的微生物群分布根据人类供体的微生物群结构进行聚类。来自CAD患者的共生梭菌和Eggerthella定植调节次级胆汁酸池，导致石胆酸和酮衍生物增加。随后，CAD小鼠胆汁酸失衡抑制肝脏胆汁酸合成，导致循环胆固醇升高。此外，来自CAD患者的粪便微生物群在转录组水平和通过增强的细胞因子分泌引起异常免疫应答的显著诱导。此外，属于CAD的微生物通过促进固有层Th 17/Treg失衡和恶化肠道屏障通透性来促进肠道炎症。总之，我们的研究结果阐明了肠道微生物群通过调节胆汁酸来影响胆固醇稳态。此外，CAD相关细菌群落被证明是全身炎症的重要调节因子，并影响动脉硬度。
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. 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. 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. 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.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
2.1
作者：
Fukiya, Satoru;Arata, Miki;Yokota, Atsushi
通讯作者：
Yokota, Atsushi
影响因子：
17.1
作者：
De Palma, Giada;Lynch, Michael D. J.;Bercik, Premysl
通讯作者：
Bercik, Premysl
影响因子：
--
作者：
Chen X;Lou G;Meng Z;Huang W
通讯作者：
Huang W
影响因子：
4.6
作者：
Baars A;Oosting A;Lohuis M;Koehorst M;El Aidy S;Hugenholtz F;Smidt H;Mischke M;Boekschoten MV;Verkade HJ;Garssen J;van der Beek EM;Knol J;de Vos P;van Bergenhenegouwen J;Fransen F
通讯作者：
Fransen F