Xu Song-Song, Zhang Xiu-Ling, Liu Sha-Sha, Feng Shu-Tang, Xiang Guang-Ming, Xu Chang-Jiang, Fan Zi-Yao, Xu Kui, Wang Nan, Wang Yue, Che Jing-Jing, Liu Zhi-Guo, Mu Yu-Lian, Li Kui
State Key Laboratory of Animal Nutrition and Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.
Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
Front Nutr. 2022 Feb 23;9:807118. doi: 10.3389/fnut.2022.807118. eCollection 2022.
The diet-induced gut microbiota dysbiosis has been suggested as a major risk factor for atherothrombosis, however, the detailed mechanism linking these conditions is yet to be fully understood.
We established a long-term excessive-energy diet-induced metabolic syndrome (MetS) inbred Wuzhishan minipig model, which is characterized by its genetic stability, small size, and human-like physiology. The metabolic parameters, atherosclerotic lesions, gut microbiome, and host transcriptome were analyzed. Metabolomics profiling revealed a linkage between gut microbiota and atherothrombosis.
We showed that white atheromatous plaque was clearly visible on abdominal aorta in the MetS model. Furthermore, using metagenome and metatranscriptome sequencing, we discovered that the long-term excessive energy intake altered the local intestinal microbiota composition and transcriptional profile, which was most dramatically illustrated by the reduced abundance of SCFAs-producing bacteria including Bacteroides, Lachnospiraceae, and Ruminococcaceae in the MetS model. Liver and abdominal aorta transcriptomes in the MetS model indicate that the diet-induced gut microbiota dysbiosis activated host chronic inflammatory responses and significantly upregulated the expression of genes related to arachidonic acid-dependent signaling pathways. Notably, metabolomics profiling further revealed an intimate linkage between arachidonic acid metabolism and atherothrombosis in the host-gut microbial metabolism axis.
These findings provide new insights into the relationship between atherothrombosis and regulation of gut microbiota via host metabolomes and will be of potential value for the treatment of cardiovascular diseases in MetS.
饮食诱导的肠道微生物群失调被认为是动脉粥样硬化血栓形成的主要危险因素，然而，将这些情况联系起来的详细机制尚未完全明确。
我们建立了一种长期高能量饮食诱导的代谢综合征（MetS）近交五指山小型猪模型，其特点是遗传稳定性、体型小以及生理特征与人类相似。对代谢参数、动脉粥样硬化病变、肠道微生物群和宿主转录组进行了分析。代谢组学分析揭示了肠道微生物群与动脉粥样硬化血栓形成之间的联系。
我们发现，在MetS模型的腹主动脉上清晰可见白色动脉粥样斑块。此外，通过宏基因组和宏转录组测序，我们发现长期高能量摄入改变了局部肠道微生物群组成和转录谱，这在MetS模型中表现为产生短链脂肪酸的细菌丰度降低，包括拟杆菌属、毛螺菌科和瘤胃球菌科。MetS模型中的肝脏和腹主动脉转录组表明，饮食诱导的肠道微生物群失调激活了宿主的慢性炎症反应，并显著上调了与花生四烯酸依赖性信号通路相关基因的表达。值得注意的是，代谢组学分析进一步揭示了花生四烯酸代谢与宿主-肠道微生物代谢轴中动脉粥样硬化血栓形成之间的密切联系。
这些发现为动脉粥样硬化血栓形成与通过宿主代谢组对肠道微生物群的调节之间的关系提供了新的见解，对治疗MetS中的心血管疾病具有潜在价值。
