High fiber diet attenuate the inflammation and adverse remodeling of myocardial infarction via modulation of gut microbiota and metabolites

Figure 1. High fiber diet alleviates myocardial infarction and left ventricular remodeling in mice. (A) Survival rate of control diet or high fiber diet treated mice after MI. (B) Heart/body weight ratios of sham-control, sham-fiber, MI control and MI fiber mice 4 weeks post operation (n = 6). (C) Representative echocardiography M-mode images of control diet or high fiber diet treated animals 1 and 4 week following operation. (D,E) Quantitative analysis of EF% (D) and FS% (E) measured by echocardiography 1 and 4 week following MI (n = 8). (F,G) Quantitative analysis of LVIDd (F) and LVIDs (G) measured by echocardiography 1 and 4 week following MI (n = 8). (H) Representative images of HE stained heart tissues 4 weeks following MI. Scale bar = 500 μM. (I) Quantification of infarct area (%) within the ischemic heart in (H) (n = 5). (J) Representative images of WGA staining of peri-infarct zone 4 weeks post MI. Scale bar = 20 μM. (K) Quantitative analysis of cardiomyocyte cross-sectional area in (J) (n = 5). (L) Representative images of Masson’s trichrome stained peri-infarct zone from control diet or high fiber diet mice 4 weeks following MI. Scale bar = 50 μM. (M) Quantification of…

Figure 2. High fiber diet attenuates inflammation, prevents monocytes infiltration and promotes macrophage polarization following MI in mice. (A–C) Concentration of cytokines IL-6 (A), IL-1β (B), and TNF-α (C) in serum 1 and 4 week following MI. (D) Representative flow cytometry plots showing the gating strategy used to determine total monocytes (CD11b+Ly6C+), Ly6Chigh monocytes (CD11b+Ly6Chigh), Ly6Cint monocytes (CD11b+ Ly6Cintermediate) and Ly6Clow monocytes (CD11b+ Ly6Clow) in peripheral blood 7 days following operation. (E–H) Quantification of total monocytes (E), Ly6Chigh monocytes (F), Ly6Cint monocytes (G) and Ly6Clow monocytes (H) in peripheral blood of control diet or high fiber diet treated mice 7 days following operation (n = 5). (I) Representative flow cytometry plots for cardiac tissue in control diet or high fiber diet treated mice 7 days post operation. Live cells were first gated with CD11b and F4/80 positive (CD11b+F4/80+) population to identify macrophages. Macrophage were then gated into iNOS+CD206− population and iNOS−CD206+ population, which represent M1 phenotype and M2 phenotype, respectively. (J–L) Pooled flow cytometry data from I (n = 4). Graphs depict mean ± SD.…

Figure 3. High fiber diet alters the composition of the gut microbial community. (A) Rarefaction curves of each sample. (B) Bacterial α-diversity estimated by Shannon’s diversity among groups. (C) Samples’ clustering result (Description, Beta unweighted_unifrac). (D) Bacterial β-diversity of principal coordinates analysis (PCoA) based on unweighted_unifrac distance indicated a distinctive distribution of the colonic microbial communities among all groups. (E) Anosim similarity analysis based on unweighted_unifrac distance rarefaction curves of each sample. (F) Heat map depicting gut microbial composition at phylum level. (G) Relative abundance of significantly different taxa at phylum level. (H,I) Proportion and relative abundance of different taxa at family level. (J) Proportion of different taxa at genus level. Sham control, n = 4; Sham fiber, n = 8; MI control, n = 5; MI fiber, n = 9. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Figure 4. High fiber diet alters gut derived metabolites. (A,B) Principal component analysis analysis (A) and partial least squares discriminant analysis analysis (B) showed a distinctive metabolites composition among four groups. (C) Heat map depicting global metabolomic profiles among four groups. (D–G) Volcano plot disclosing the differences in metabolites between two groups in following ways: sham control vs. MI control (D), sham fiber vs. MI fiber (E), sham fiber vs. sham control (F) and MI control vs. MI fiber (G). (H–K) Bubble chart distributing significantly different associated metabolic pathway between fiber diet groups and control diet groups in positive ions mode (H,I) and negative ions mode (J,K). Sham control, n = 6; Sham fiber, n = 8; MI control, n = 8; MI fiber, n = 10.