Blood Microbiota Modification After Myocardial Infarction Depends Upon Low-Density Lipoprotein Cholesterol Levels

Abstract

Background The role of bacteria on the onset of cardiovascular disease has been suggested. Reciprocally, increased intestinal bacterial translocation and bloodstream infection are common comorbidities associated with heart failure and myocardial infarction (MI). In this context, the aim of this study was to analyze the blood microbiome in patients shortly after acute myocardial infarction. Methods and Results We carried out a case control study comparing 103 patients at high cardiovascular risk but free of coronary disease and 99 patients who had an MI. The blood microbiome was analyzed both quantitatively by 16S quantitative polymerase chain reaction and qualitatively by 16S targeted metagenomic sequencing specifically optimized for blood samples. A significant increase in blood bacterial 16S rDNA concentration was observed in patients admitted for MI. This increase in blood bacterial DNA concentration was independent of post-MI left ventricular function and was more marked in patients with low-density lipoprotein cholesterol ≥1 g/L. In addition, differences in the proportion of numerous bacterial taxa in blood were significantly modified with the onset of MI, thus defining a blood microbiota signature of MI. Among the bacterial taxa whose proportions are decreased in patients with MI, at least 6 are known to include species able to metabolize cholesterol. Conclusions These results could provide the basis for the identification of blood microbiome-based biomarkers for the stratification of MI patients. Furthermore, these findings should provide insight into the mechanism underlying the negative correlation reported between low-density lipoprotein cholesterol concentration and the prognosis at the acute onset of MI and mortality. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02405468.

Keywords: bacteria; blood metagenomics; blood microbiota; cholesterol; myocardial infarction.

Figure 1

Modifications of blood bacterial 16S rDNA concentration and diversity differentiate patients who had an MI. A, Mean concentrations (bar plot) and individual values (dot plot) of bacterial 16S rDNA assessed by qPCR in patients after MI or control patients. B, Mean concentrations (bar plots) and individual values (dot plots) of bacterial diversity (Shannon index) assessed by 16S metagenomic sequencing in patients after MI or control patients (*P<0.05; **P<0.01; ****P<0.0001). MI indicates myocardial infarction; qPCR, quantitative polymerase chain reaction.

Figure 2

Specific blood bacterial profiles assessed by 16S metagenomic sequencing characterize patients who had an MI. A, Mean relative proportions of bacterial phyla in blood of the overall study population. B, LEfSe analysis of the blood bacterial taxa correlated (red) or inversely correlated (green) with MI status. The cladograms represented here display all bacterial taxa sorter by phylogenic levels (from phyla at the center to genus at the outside rim). The bacterial taxa that are significantly different (P<0.05 with Mann–Whitney test) between the 2 groups being compared are displayed in green when more present in the control patients and in red when more present in the case patients. LEfSe, linear discriminant analysis effect size; MI, myocardial infarction.

Figure 3

Modification of proportions of blood bacterial taxa assessed by 16S metagenomic sequencing characterizes patients who had an MI. Mean (bar plots) and individual values (dot plots) of relative proportions of relevant blood bacterial taxa in patients after MI or control patients (*P<0.05; **P<0.01; ***P<0.001). MI indicates myocardial infarction.

Figure 4

Cholesterol‐degrading bacteria are decreased in patients with MI. A, Mean (bar plots) and individual values (dot plots) of relative proportions of blood bacterial taxa known to degrade cholesterol in patients after myocardial infarction or control patients. B, Modification of blood bacterial 16S rDNA concentration in patients who had an MI depends on the blood LDL cholesterol concentration. Mean (bar plots) and individual values (dot plots) concentrations of bacterial 16S rDNA assessed by qPCR in patients after myocardial infarction or control patients in subgroup of patients depending of LDL cholesterol concentration (*P<0.05; **P<0.01; ***P<0.001; ****P<0.0001; ns: not significant). LDL indicates low‐density lipoprotein; MI, myocardial infarction; qPCR, quantitative polymerase chain reaction.