低密度脂蛋白受体
促炎细胞因子
炎症
胆固醇
肠道菌群
阿克曼西亚
内科学
生物
内分泌学
医学
免疫学
脂蛋白
乳酸菌
细菌
遗传学
作者
Eelke Brandsma,Niels J. Kloosterhuis,Mirjam H. Koster,Daphne Dekker,Marion J. Gijbels,Saskia van der Velden,Melany Ríos-Morales,Martijn J.R. van Faassen,Marco G. Loreti,Alain de Bruin,Jingyuan Fu,Folkert Kuipers,Barbara M. Bakker,Marit Westerterp,Menno P.J. de Winther,Marten H. Hofker,Bart van de Sluis,Debby P. Y. Koonen
出处
期刊:Circulation Research
[Ovid Technologies (Wolters Kluwer)]
日期:2019-01-04
卷期号:124 (1): 94-100
被引量:222
标识
DOI:10.1161/circresaha.118.313234
摘要
Rationale: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between gut microbiota, inflammation, and atherosclerosis has not been explored previously. Objective: Here, we investigated whether a proinflammatory microbiota from Caspase1 −/− ( Casp1 −/− ) mice accelerates atherogenesis in Ldlr −/− mice. Method and Results: We treated female Ldlr −/− mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1 −/− mice based on a cohousing approach. Autologous transplantation of fecal microbiota of Ldlr −/− mice served as control. Mice were cohoused for 8 or 13 weeks and fed chow or high-fat cholesterol–rich diet. Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health, and atherosclerotic phenotypes were measured. Unweighted Unifrac distances of 16S rDNA (ribosomal DNA) sequences confirmed the introduction of the Casp1 −/− and Ldlr −/− microbiota into Ldlr −/− mice (referred to as Ldlr −/− ( Casp1 −/− ) or Ldlr −/− ( Ldlr −/− ) mice). Analysis of atherosclerotic lesion size in the aortic root demonstrated a significant 29% increase in plaque size in 13-week high-fat cholesterol–fed Ldlr −/− ( Casp1 −/− ) mice compared with Ldlr −/− ( Ldlr −/− ) mice. We found increased numbers of circulating monocytes and neutrophils and elevated proinflammatory cytokine levels in plasma in high-fat cholesterol–fed Ldlr −/− ( Casp1 −/− ) compared with Ldlr −/− ( Ldlr −/− ) mice. Neutrophil accumulation in the aortic root of Ldlr −/− ( Casp1 −/− ) mice was enhanced compared with Ldlr −/− ( Ldlr −/− ) mice. 16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid–producing taxonomies Akkermansia , Christensenellaceae , Clostridium , and Odoribacter in Ldlr −/− ( Casp1 −/− ) mice. Consistent with these findings, cumulative concentrations of the anti-inflammatory short-chain fatty acids propionate, acetate and butyrate in the cecum were significantly reduced in 13-week high-fat cholesterol–fed Ldlr −/− ( Casp1 −/− ) compared with Ldlr −/− ( Ldlr −/− ) mice. Conclusions: Introduction of the proinflammatory Casp1 −/− microbiota into Ldlr −/− mice enhances systemic inflammation and accelerates atherogenesis.
科研通智能强力驱动
Strongly Powered by AbleSci AI