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.
Highlights
Atherosclerosis (AS) is a diffuse, slowly progressing disease that affects large- and medium-sized arteries
differentially expressed gene (DEG) and related functional annotation analyses were conducted based on a messenger RNA microarray dataset (GSE43292) to explore the differences between Carotid atherosclerosis (CAS) patients and healthy controls from a transcriptomic level
Correlation analyses were performed between differentially enriched microbiota, metabolites, and DEGs to integrate omics
Summary
Atherosclerosis (AS) is a diffuse, slowly progressing disease that affects large- and medium-sized arteries. Advanced atherosclerotic plaques can invade the arterial lumen, impeding blood flow, and resulting in tissue ischemia (Faxon et al, 2004; Libby et al, 2019). Carotid atherosclerosis (CAS) is a preventable cause of 20–30% of stroke, approximately 21% of people aged 30–79 years have carotid plaque, and 1.5% have carotid stenosis (Petty et al, 2000; Song et al, 2020). Carotid atherosclerosis (CAS) is an important cause of stroke. Interactions between the gut microbiome and metabolome have been widely investigated with respect to the pathogenesis of cardiovascular diseases, information regarding CAS remains limited
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