The identification of metabolites from gut microbiota in coronary heart disease via network pharmacology

Abstract

Although the gut microbial metabolites exhibit potential effects on coronary heart disease (CHD), the underlying mechanism remains unclear. In this study, the active gut microbial metabolites acting on CHD and their potential mechanisms of action were explored through a network pharmacological approach. We collected a total of 208 metabolites from the gutMgene database and 726 overlapping targets from the similarity ensemble approach (SEA) and SwissTargetPrediction (STP) database, and ultimately identified 610 targets relevant to CHD. In conjunction with the gutMGene database, we identified 12 key targets. The targets of exogenous substances were removed, and 10 core targets involved in CHD were eventually retained. The microbiota–metabolites–targets–signalling pathways network analysis revealed that C-type lectin receptor signalling pathway, Lachnospiraceae, Escherichia, mitogen-activated protein kinase 1, prostaglandin-endoperoxidase synthase 2, phenylacetylglutamine and alcoholic acid are notable components of CHD and play important roles in the development of CHD. The results of molecular docking experiments demonstrated that AKT1-glycocholic acid and PTGS2-phenylacetylglutamine complexes may act on C-type lectin receptor signalling pathways. In this study, the key substances and potential mechanisms of gut microbial metabolites were analysed via network pharmacological methods, and a scientific basis and comprehensive idea were provided for the effects of gut microbial metabolites on CHD.

Keywords:

• Coronary heart disease
• network pharmacology
• Lachnospiraceae
• Escherichia
• phenylacetylglutamine
• glycocholic acid

Author contributions

Conceiving and designing the full experiments: S.-J. Y. and Y.-P. T.; methodology, H.-M. Z. and S.-J. Y.; software, X.-Y. Y. and W.-X. W.; performing the experiments: H.-M. Z.; data analysis, H.-M. Z., S.-J. Y., X.-Y. Y, W.-X. W., Q. Z., D.-Q. X., J.-J. L. and Y.-P. T.; writing and editing original draft preparation, H.-M. Z. and X.-Y. Y.; funding acquisition, S.-J. Y. and Y.-P. T. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analysed during this study are included in this published article (and its Supplementary Information Files).

Additional information

Funding

This research was funded by the National Natural Science Foundation of China (81903786), the Natural Science Foundation of Shaanxi Province (2022SF-221) and Subject Innovation Team of Shaanxi University of Chinese Medicine (2019-YL10).