Chen Jingfeng, Qin Qian, Yan Su, Yang Yang, Yan Hang, Li Tiantian, Wang Lin, Gao Xinxin, Li Ang, Ding Suying
Health Management Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
College of Public Health, Zhengzhou University, Zhengzhou, China.
Front Cardiovasc Med. 2021 Nov 19;8:739093. doi: 10.3389/fcvm.2021.739093. eCollection 2021.
Carotid atherosclerosis (CAS) is a reflection of systemic atherosclerosis and the main pathological processes of cardiovascular disease (CVD), namely, carotid intima-media thickening, carotid plaque formation, and carotid stenosis. Accumulating evidence indicates that the gut microbiota plays an important role in CVD and gut-brain disorders, but the associations of the composition and metabolites of the gut microbiome with CAS have not been studied comprehensively. We performed a gut microbiome genome-wide association study in 31 patients with CAS and 51 healthy controls using whole-genome shotgun sequencing. We found that several risk factors (waist circumference, body mass index, diastolic blood pressure, systolic blood pressure, fasting blood glucose, glycated hemoglobin A1c, total cholesterol, triglyceride, and low-density lipoprotein cholesterol) and inflammatory markers (white blood cell count and absolute value of neutrophils) were significantly higher in the CAS group than in the control group. In addition, 21 species and 142 pathways were enriched in the CAS group, and 10 species and 1 pathway were enriched in the control group. Specifically, , and were the most abundant species in the CAS group, whereas , and were the most abundant species in the control group. Finally, we found that most gut microbes and microbial pathways that were enriched in the CAS group had significant positive correlations with clinical characteristics, whereas the microbes and pathways enriched in healthy controls had significant negative correlations with clinical characteristics excluding high-density lipoprotein cholesterol. In addition, the associations between gut microbes and some microbial pathways (short-chain fatty acid, lipopolysaccharide, and menaquinol biosynthesis) were identified. Our results indicate the existence of a cyclic pathway that elevates the circulating concentrations of trimethylamine-N-oxide in patients with CAS but reduces its concentrations in healthy controls.
颈动脉粥样硬化（CAS）是全身动脉粥样硬化的一种表现，也是心血管疾病（CVD）的主要病理过程，即颈动脉内膜中层增厚、颈动脉斑块形成和颈动脉狭窄。越来越多的证据表明，肠道微生物群在心血管疾病和肠脑疾病中起重要作用，但肠道微生物组的组成和代谢产物与CAS之间的关联尚未得到全面研究。我们使用全基因组鸟枪法测序对31例CAS患者和51例健康对照进行了肠道微生物组全基因组关联研究。我们发现，CAS组的几个风险因素（腰围、体重指数、舒张压、收缩压、空腹血糖、糖化血红蛋白A1c、总胆固醇、甘油三酯和低密度脂蛋白胆固醇）和炎症标志物（白细胞计数和中性粒细胞绝对值）显著高于对照组。此外，CAS组有21个物种和142条通路富集，对照组有10个物种和1条通路富集。具体而言， 、 和 是CAS组中最丰富的物种，而 、 和 是对照组中最丰富的物种。最后，我们发现，CAS组中富集的大多数肠道微生物和微生物通路与临床特征呈显著正相关，而健康对照组中富集的微生物和通路与除高密度脂蛋白胆固醇外的临床特征呈显著负相关。此外，还确定了肠道微生物与一些微生物通路（短链脂肪酸、脂多糖和甲基萘醌生物合成）之间的关联。我们的结果表明，存在一种循环途径，该途径会提高CAS患者血液中氧化三甲胺的循环浓度，但会降低健康对照者血液中氧化三甲胺的浓度。
