Insights from metagenomics into gut microbiome associated with acute coronary syndrome therapy

Abstract

Acute coronary syndrome (ACS) is a predominant cause of mortality, and the prompt and precise identification of this condition is crucial to minimize its impact. Recent research indicates that gut microbiota is associated with the onset, progression, and treatment of ACS. To investigate its role, we sequenced the gut microbiota of 38 ACS patients before and after percutaneous coronary intervention and statin therapy at three time points, examining differential species and metabolic pathways. We observed a decrease in the abundance of Parabacteroides, Escherichia, and Blautia in patients after treatment and an increase in the abundance of Gemalla, Klebsiella variicola, Klebsiella pneumoniae, and others. Two pathways related to sugar degradation were more abundant in patients before treatment, possibly correlated with disorders of sugar metabolism and risk factors, such as hyperglycemia, insulin resistance, and insufficient insulin secretion. Additionally, seven pathways related to the biosynthesis of vitamin K2 and its homolog were reduced after treatment, suggesting that ACS patients may gradually recover after therapy. The gut microbiota of patients treated with different statins exhibited notable differences after treatment. Rosuvastatin appeared to promote the growth of anti-inflammatory bacteria while reducing pro-inflammatory bacteria, whereas atorvastatin may have mixed effects on pro-inflammatory and anti-inflammatory bacteria while increasing the abundance of Bacteroides. Our research will provide valuable insights and enhance comprehension of ACS, leading to better patient diagnosis and therapy.

Keywords: acute coronary syndrome; gut microbiota; intestinal; metabolism; metagenome; statin.

Figure 1

Alterations in gut microbiota among the four groups. (A) α-diversity (Shannon index) among the four groups was analyzed at the phylum, genus and species levels. (B) Constrained Principal Coordinates Analysis (CPCoA) of Euclidean distance on all samples based on species level. PERMANOVA test was used to detect the independent effects of clinical features on microbial community (Euclidean distance). (C) Correlation of clinical indicators and gut microbiota. R-square statistics were presented on each cell. Clinical features included subject, age, sex, TG, triglycerides; Chol, cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ALB, albumin; Cr, Creatinine; cTnT, cardiac troponin T; BNP, B-type natriuretic peptides; HbA1c, hemoglobin A1c. (D) Relative abundance of gut microbiota on phylum, genus, and species levels in ACS patients at three time points. (E) Venn diagram on species level in individuals from various stages. (F) Biomarkers of ACS patients at different stages of treatment (LDA score threshold >2). (G) Differential species between healthy controls and ACS patients before treatment (*adjust p < 0.05, **adjust p < 0.01, and ***adjust p < 0.001, t-test, Benjamini–Hochberg FDR).

Figure 2

Alterations of functional pathways in ACS patients before and after treatment. (A) Venn diagram of metabolic pathways in ACS samples from various stages. (B) Significantly differential pathways of ACS patients before and after treatment (*adjust p < 0.05, **adjust p < 0.01, and ***adjust p < 0.001, Kruskal–Wallis test, Benjamini–Hochberg FDR). (C) Association between microbiome composition and metabolic pathways. Correlation values (Spearman) were presented on each cell by various colors and significance also emerged (*p < 0.05, **p < 0.01, and ***p < 0.001, t-test).

Figure 3

Alterations in gut microbiota affected by drugs. (A) α-diversity (Shannon index) of ACS patients treated by different drugs at three stages of therapy. (B) Principal Coordinates Analysis (PCoA) of patients used different medications at three stages of therapy (Bray–Curtis distance). (C) Microbiota that changed significantly after treatment with rosuvastatin. (D) Microbiota that changed significantly after treatment with atorvastatin (*adjust p < 0.05, **adjust p < 0.01, and ***adjust p < 0.001, Kruskal–Wallis test, Benjamini–Hochberg FDR).

Figure 4

Alterations in gut microbiota affected by drugs. (A) Differential species in groups atorvastatin and rosuvastatin before treatment. (B) Differential species in groups atorvastatin and rosuvastatin one month after treatment. (C) Differential species in groups atorvastatin and rosuvastatin 2 month after treatment (t-test, Benjamini–Hochberg FDR).