| OBJECTIVE:Recently,with the deeper understanding of human gut microbiome,researchers have found that it is extensively correlated with cardiovascular and metabolic diseases.Regulation of gut microbiome may help treat such diseases.Coronary artery disease with diabetes is a clinical condition which requires more attention and further research.The objective of this study was to clarify the gut microbial and metabolic characteristics of this population,providing direction for further mechanism research.METHODS:From December 2016 to June 2018,we consecutively enrolled 109 patients with stable coronary artery disease,of whom 38 have type 2 diabetes,and 55 healthy controls in strict accordance with the exclusion criteria.We collected demographic information,baseline clinical data from all subjects,and collected subjects' feces and blood samples according to standard procedures for metagenomic sequencing and non-targeted metabolomics.We integrate all of the above information for bioinformatics and statistical analysis.RESULTS:Based on metagenomic sequencing,we clarified that the alpha-diversity of gut microbiome in patients with stable coronary artery disease was reduced.The composition of gut microbiome in patients with stable coronary heart disease with type 2 diabetes was significantly different from that of patients with only stable coronary artery disease and healthy controls,including the increased relative abundance of Proteobacteria,Aclinbacteria,Klebsiella,Escherichia,Lactobacillus,Bifidobacterium,and decreased relative abundance of Roseburia and Eubacterium.We also found 67 differential metagenomic species(MGS)among groups and established a network of associations among them.Functionally,we discovered that the characteristics of the gut microbiome in patients of stable coronary artery disease with type 2 diabetes are mainly related to the enhancement of membrane transport-related and type IV secretion functions.Subsequently,we found four MGS mainly of Bacteroidetes enriched in patients of stable coronary artery disease with type 2 diabetes have positive correlation with metabolites like glycerolipids and cholesterol esters,thus furtherly correlated with clinical phenotypes such as fasting blood glucose and HOMA-IR.Five MGS of Firmicutes enriched in patients with only stable coronary artery disease show negative correlation with diabetes-related clinical phenotypes indirectly.Discussion:The gut microbiome of patients of stable coronary artery disease with type 2 diabetes has certain characteristics in its composition and function,which are different from patients with only stable coronary artery disease.Our study identified important differential species and metabolites and established their associations with clinical phenotypes related to diabetes.These findings deepen our understanding of the particular clinical situation of coronary artery disease with diabetes,and also provide a new direction for further research on coronary artery disease with type 2 diabetes and mechanisms of the microbiome-host interaction. |
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