Table_8_Exploration of Crucial Mediators for Carotid Atherosclerosis Pathogenesis Through Integration of Microbiome, Metabolome, and Transcriptome.DOCX

BackgroundCarotid atherosclerosis (CAS) is an important cause of stroke. Although interactions between the gut microbiome and metabolome have been widely investigated with respect to the pathogenesis of cardiovascular diseases, information regarding CAS remains limited.Materials and MethodsWe utilized 16S ribosomal DNA sequencing and untargeted metabolomics to investigate the alterations in the gut microbiota and plasma metabolites of 32 CAS patients and 32 healthy controls. The compositions of the gut microbiota differed significantly between the two groups, and a total of 11 differentially enriched genera were identified. In the metabolomic analysis, 11 and 12 significantly changed metabolites were screened in positive (POS) and negative (NEG) modes, respectively. α-N-Phenylacetyl-L-glutamine was an upregulated metabolite in CAS patients detected in both POS and NEG modes and had the highest | log2(fold change)| in POS mode. In addition, transcriptomic analysis was performed using the GSE43292 dataset.ResultsA total of 132 differentially expressed genes (DEGs) were screened. Among the upregulated DEGs in CAS patients, FABP4 exhibited the highest | log2(fold change)|. Furthermore, FABP4 was positively associated with Acidaminococcus and had the highest Spearman’s correlation coefficient and the most significant p-value among the microbiota–DEG pairs.ConclusionIn this study, we investigated the potential “microbiota–metabolite–gene” regulatory axis that may act on CAS, and our results may help to establish a theoretical basis for further specialized study of this disease.

背景：颈动脉粥样硬化（CAS）是中风的重要原因。尽管肠道微生物群和代谢组与心血管疾病发病机制之间的相互作用已得到广泛研究，但关于CAS的信息仍然有限。材料与方法：本研究利用16S核糖体DNA测序和靶向代谢组学技术，对32名CAS患者和32名健康对照者的肠道微生物组和血浆代谢物进行了研究。两组肠道微生物组的组成存在显著差异，共鉴定出11个富集差异显著的菌属。在代谢组学分析中，分别从阳性（POS）和阴性（NEG）模式中筛选出11和12个显著变化的代谢物。α-苯乙酰-L-谷氨酰胺在CAS患者中检测到，其在POS和NEG模式中均为上调代谢物，且在POS模式中具有最高的|log2(变化倍数)|。此外，还使用GSE43292数据集进行了转录组学分析。结果：共筛选出132个差异表达基因（DEGs）。在CAS患者中，上调的DEGs中FABP4表现出最高的|log2(变化倍数)|。此外，FABP4与Acidaminococcus呈正相关，在微生物群-DEG对中具有最高的Spearman相关系数和最显著的p值。结论：本研究旨在探讨可能作用于CAS的“微生物群-代谢物-基因”调控轴，研究结果可能有助于为该疾病的进一步专门研究奠定理论基础。