Abstract
Background: Cigarette smoking has been considered a modifiable risk factor for coronary artery disease (CAD). Changes in gut microbiota and microbe-derived metabolites have been shown to influence atherosclerotic pathogenesis. However, the effect of cigarette smoking on the gut microbiome and serum metabolites in CAD remains unclear.Method: We profiled the gut microbiota and serum metabolites of 113 male participants with diagnosed CAD including 46 current smokers, 34 former smokers, and 33 never smokers by 16S ribosomal RNA (rRNA) gene sequencing and untargeted metabolomics study. A follow-up study was conducted. PICRUSt2 was used for metagenomic functional prediction of important bacterial taxa.Results: In the analysis of the microbial composition, the current smokers were characterized with depleted Bifidobacterium catenulatum, Akkermansia muciniphila, and enriched Enterococcus faecium, Haemophilus parainfluenzae compared with the former and never smokers. In the untargeted serum metabolomic study, we observed and annotated 304 discriminant metabolites, uniquely including ceramides, acyl carnitines, and glycerophospholipids. Pathway analysis revealed a significantly changed sphingolipids metabolism related to cigarette smoking. However, the change of the majority of the discriminant metabolites is possibly reversible after smoking cessation. While performing PICRUSt2 metagenomic prediction, several key enzymes (wbpA, nadM) were identified to possibly explain the cross talk between gut microbiota and metabolomic changes associated with smoking. Moreover, the multi-omics analysis revealed that specific changes in bacterial taxa were associated with disease severity or outcomes by mediating metabolites such as glycerophospholipids.Conclusions: Our results indicated that both the gut microbiota composition and metabolomic profile of current smokers are different from that of never smokers. The present study may provide new insights into understanding the heterogenic influences of cigarette smoking on atherosclerotic pathogenesis by modulating gut microbiota as well as circulating metabolites.
Highlights
Cigarette smoking is a major modifiable cardiovascular risk factor [1]
A total of 113 male participants who were diagnosed with coronary artery disease (CAD) at admission were consecutively enrolled at Peking Union Medical College Hospital (PUMCH) and were further divided into the following three groups based on their smoking status: current smokers (N = 46), former smokers (N = 34), and never smokers (N = 33)
Our study demonstrated that smoking can influence the physical condition of patients with CAD from a multi-omics perspective
Summary
Cigarette smoking is a major modifiable cardiovascular risk factor [1]. Smoking cessation in patients with CAD can substantially lower the risk of recurrent cardiovascular events and all-cause mortality [4]. In the last few decades, there has been a surge of interest in the pathophysiologic role of gut microbiota in atherosclerosis and cardiovascular disease. Elevated plasma levels of TMAO were associated with an increased risk of major adverse cardiovascular events, which is independent of traditional risk factors, even in the low-risk population [9]. Cigarette smoking has been considered a modifiable risk factor for coronary artery disease (CAD). Changes in gut microbiota and microbe-derived metabolites have been shown to influence atherosclerotic pathogenesis. The effect of cigarette smoking on the gut microbiome and serum metabolites in CAD remains unclear
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