Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice

Abstract

Physical exercise is commonly regarded as protective against cardiovascular disease (CVD). Recent studies have reported that exercise alters the gut microbiota and that modification of the gut microbiota can influence cardiac function. Here, we focused on the relationships among exercise, the gut microbiota and cardiac function after myocardial infarction (MI). Four-week-old C57BL/6J mice were exercised on a treadmill for 4 weeks before undergoing left coronary artery ligation. Cardiac function was assessed using echocardiography. Gut microbiomes were evaluated post-exercise and post-MI using 16S rRNA gene sequencing on an Illumina HiSeq platform. Exercise training inhibited declines in cardiac output and stroke volume in post-MI mice. In addition, physical exercise and MI led to alterations in gut microbial composition. Exercise training increased the relative abundance of Butyricimonas and Akkermansia. Additionally, key operational taxonomic units were identified, including 24 lineages (mainly from Bacteroidetes, Barnesiella, Helicobacter, Parabacteroides, Porphyromonadaceae, Ruminococcaceae, and Ureaplasma) that were closely related to exercise and cardiac function. These results suggested that exercise training improved cardiac function to some extent in addition to altering the gut microbiota; therefore, they could provide new insights into the use of exercise training for the treatment of CVD.

Keywords: 16S rRNA; cardiac function; exercise; gut microbiome; myocardial infarction.

FIGURE 1

Timeline of the study. Mice were subjected to exercise or allowed to remain sedentary in cages for 4 weeks before they underwent a coronary artery ligation or sham operation. Fecal samples were collected and echocardiography was performed 1 week after the operation.

FIGURE 2

Cardiac function in exercise-trained mice after myocardial infarction. The ratio of heart weight/body weight and lung weight/body weight in mice subjected to left coronary artery ligation (A,B), and the results of echocardiography in post-MI mice, including (C) ejection fraction (EF), (D) fractional shortening (FS), (E) left ventricular end-systolic diameter (LVESD), (F) cardiac output (CO) and (G) stroke volume (SV). ^∗P < 0.05 compared to the corresponding groups.

FIGURE 3

Comparison of the microbial community in the non-surgery, sham and MI mice based on uniFrac distances obtained in a PCoA analysis. Unweighted_uniFrac distances among the exercise-trained group (blue), the negative control group (red), the sham-control group (green), the sham-exercise-trained group (light blue), the MI-exercise-trained group (yellow) and the MI-control group (purple).

FIGURE 4

Dissimilarity in microbial community structure following MI between the non-surgery groups and the sham groups. UniFrac distances were determined to describe the dissimilarity between the non-surgery and sham groups and between the MI and sham groups in (A) non-exercise-trained and (B) exercise-trained mice (independent samples t-test).

FIGURE 5

Relative abundance and LEfSE in the bacterial community structure in the non-surgery, sham and MI groups. Relative abundance of major genera in bacterial communities among the (A) non-surgery, (C) sham and (E) MI groups. Differential features were selected according to LEfSE between the exercise-trained and control mice in the (B) non-surgery, (D) sham and (F) MI groups.

FIGURE 6

Beta diversity of the gut microbial community among various parameters of cardiac function. FS, fractional shortening; EF, ejection fraction; LVESD, left ventricular end-systolic diameter; CO, cardiac output; SV, stroke volume; HW/BW, the ratio of heart weight/body weight; LW/BW, the ratio of lung weight/body weight. The R² value represents the results of Adonis. ^∗P < 0.05, ^∗∗P < 0.01.

FIGURE 7

Correlations between cardiac function and the relative abundance of certain bacterial taxa. Correlations between the relative abundance of taxa and echocardiographic parameters: (A) left ventricular end systolic diameter, (B) left ventricular ejection fraction, (C) cardiac output, and (D) stroke volume (Spearman’s rank correlation).

FIGURE 8

Heat map representing the important OTUs and their relationships with heart function and exercise. A total of 24 key variables were found to be significantly correlated with exercise or cardiac function (Spearman’s rank correlation). The symbols “+” and “-” represent positive and negative correlations among exercise, LVESD, SV, and EF.