Exploration of Crucial Mediators for Carotid Atherosclerosis Pathogenesis Through Integration of Microbiome, Metabolome, and Transcriptome

Abstract

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.

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis and Phenotyping of Carotid Artery Stenosis

“…More importantly, without homeostatic control urine have the potential to detect the small and early pathological changes (Wu and Gao, 2015;Wu et al, 2021). Mass spectrum-based omics methods have been used in the biomarker discovery of CAS, and the sample source mainly contained blood or atherosclerosis plaque (Vorkas et al, 2016;Li et al, 2017;Lee et al, 2019;Ji et al, 2021). Until now, there is still no available urinary biomarker for CAS.…”

Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics

“…To compare the differences in plasma metabolites between AAA and AS, 32 AAA and 32 AS patients were included in this study. The clinical characteristics of these participants are shown in Table 1 (Ji et al, 2021). Patients with AAA were slightly older (P=0.019), but there were no differences in gender, body mass index (BMI), or underlying diseases such as hypertension and diabetes, which would affect metabolism.…”

Gut Microbiota and Atherosclerosis—Focusing on the Plaque Stability

“…In recent years, several studies have confirmed the presence of bacterial DNA in atherosclerotic plaque which may contribute to the development of cardiovascular disease (52). In addition, researchers have also found that compared with people without atherosclerosis, the patients with atherosclerosis (Table 1) showed some differences in the gut microbiota (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)53). Garshick et al donated aortas of Apoe-/-mice with atherosclerosis into normolipidemic wild-type mice, then feeding antibiotic.…”

“…Ji et al once found that Acidaminococcus was more abundant in the CAS patient. Acidaminococcus was once often enriched in patients with several inflammatory diseases and positively correlated with a proinflammatory diet, which may indicate that Acidaminococcus was a proinflammatory microbiota and represent inflammatory status in the development of AS ( 18 ). In atherosclerotic plaques, phylum Proteobacteria dominated and the phylum Firmicutes , predominantly found in the gut, is also present in atherosclerotic plaques.…”

“…In recent years, several studies have investigated the effects of the gut microbiota on atherosclerosis and proved that there are some connections between cardiovascular events and atherosclerotic plaque characteristics (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). However, the roles of the gut microbiota in the stability of plaque are still unclear.…”