Integrated analysis reveals microbiota-metabolite-immune alterations associated with coronary heart disease.

BACKGROUND

The relationship between gut microbiota, metabolites, immune environment, and coronary heart disease (CHD) remains incompletely understood.

METHODS

This study enrolled 100 non-CHD controls and 302 CHD patients, including 102 with acute coronary syndrome (ACS), 100 with chronic stable angina pectoris (CSAP), and 100 with ischemic cardiomyopathy (ICM). Gut microbiota was analyzed via 16S rRNA gene sequencing, plasma trimethylamine N-oxide (TMAO) and phenylacetylglutamine (PAGln) were measured by mass spectrometry, and flow cytometry was used to assess T, B, and natural killer (NK) lymphocyte subsets.

RESULTS

CHD patients showed reduced gut microbial richness (Chao1 and ACE indices, p < 0.05) compared to controls, with enriched Actinomycetaceae, Streptococcaceae, Rothia Micrococcaceae, Bacilli, Dialister in CHD groups. Predicted microbial functional pathways, including glutathione metabolism, nitrogen metabolism, and porphyrin and chlorophyll metabolism, were significantly reduced in CHD patients based on PICRUSt2 analysis. PAGln levels were significantly higher in CHD especially in ACS patients than in controls (p = 0.0016), positively correlating with CHD severity (GRACE score, Spearman r = 0.243, p < 0.001), while TMAO showed no significant difference. PAGln negatively correlated with total lymphocytes, T cells, and B cells, and was associated with altered abundances of Parabacteroides, Tannerellaceae, Bacilli, and so on.

CONCLUSION

CHD is associated with gut microbiota dysbiosis, and reduced microbial richness, which may influence immune homeostasis.