The changes of gut microbiota after acute myocardial infarction in rats

Abstract

Recent studies suggested that gut microbiota was involved in the development of coronary artery disease. However, the changes of gut microbiota following acute myocardial infarction (AMI) remain unknown. In this study, a total of 66 male Wistar rats were randomly divided into control, AMI and SHAM groups. The controls (n = 6) were sacrificed after anesthesia. The AMI model was built by ligation of left anterior descending coronary artery. The rats of AMI and SHAM groups were sacrificed at 12 h, 1 d, 3 d, 7 d and 14 d post-operation respectively. Gut microbiota was analyzed by 16S rDNA high throughput sequencing. The gut barrier injuries were evaluated through histopathology, transmission electron microscope and immunohistochemical staining. The richness of gut microbiota was significantly higher in AMI group than SHAM group at 7 d after AMI (P<0.05). Principal coordinate analysis with unweighted UniFrac distances revealed microbial differences between AMI and SHAM groups at 7 d. The gut barrier impairment was also the most significant at 7 d post-AMI. We further identified the differences of microorganisms between AMI and SHAM group at 7 d. The abundance of Synergistetes phylum, Spirochaetes phylum, Lachnospiraceae family, Syntrophomonadaceae family and Tissierella Soehngenia genus was higher in AMI group compared with SHAM group at 7 d post-operation (q<0.05). Our study showed the changes of gut microbiota at day 7 post AMI which was paralleled with intestinal barrier impairment. We also identified the microbial organisms that contribute most.

Fig 1. The relative abundance of gut microbiota at phylum level in different groups (n = 6 for each column).

CON, control group; AMI, acute myocardial infarction group; SHAM, sham group.

Fig 2. The microbial changes after AMI.

(A) The richness index (including Observed species, ACE and Chao1) in different groups. The richness of AMI group was significantly higher than that of SHAM group at 7 d post-operation. ** P<0.01; *** P<0.001. (B) Principal coordinate analysis (PCoA) of gut microbiota showed that the microbial communities of AMI group at 7 d post-AMI clustered distinctly from SHAM group at 7 d. One circle represents microbiota composition (all phyla combined) in one subgroup (n = 6, one dot represents one sample). CON, control group; AMI, acute myocardial infarction group; SHAM, sham group.

Fig 3. The changes of microbial communities at 7 d after AMI.

(A) The microbial differences between AMI 7 d and SHAM 7 d group at phylum (a), family(b) and genus(c) level. The abundance difference between the two groups was showed by q value which was corrected by Benjamini discovery rate correction. * represents q<0.05, k kingdom, p phylum, o order, f family, g genus. (B) LEfSe analysis between AMI-7d and SHAM-7d group showed enrichment for Lachnospiraceae family in AMI group. CON, control group; AMI, acute myocardial infarction group; SHAM, sham group.

Fig 4. Changes of gut barrier in different groups.

(A) Histopathological examination of rats’ distal ileum. (H&E stain×100) showed mucosal injury at 7 d post-AMI. (B) Chiu pathological scores revealed markedly higher scores in AMI 7 d group. CON, control group; AMI, acute myocardial infarction group; SHAM, sham group. *P<0.05.