Metformin-mediated modulation of gut microbiota-derived trimethylamine N-oxide (TMAO) in myocardial infarction: Insights from in vivo, metabolomics, and in silico studies
Abstract
BACKGROUND
Metformin (MET) protects against cardiovascular disorders by improving endothelial function, reducing inflammation, and lowering lipid levels. It is believed to modify gut microbiota, reducing Trimethylamine N-oxide (TMAO) production, decreasing the risk of atherosclerosis and Myocardial infarction (MI). Yet, the mechanisms behind MET's ameliorative benefits on the gut microbiota and cardiovascular disease remain poorly understood.
PURPOSE
This Study focused on evaluating and understanding the mechanisms of MET in MI and gut microbiota using a combined approach of metabolomics and an in silico approach.
METHODS
MI was induced in mice with isoproterenol (ISO) in conjunction with a choline-rich diet (CH), and cardiomyocytes were subjected to ISO to replicate myocardial damage in-vivo. Using UPLC-MS/MS, all metabolic changes in the experimental mice's fecal sample were profiled. The pathway analysis findings were derived from the detected differential metabolites, and the network pharmacology technique was used to validate the results further.
RESULTS
Our research discovered that MET had beneficial effects in vivo and in vitro, as demonstrated by improvements in various biochemical markers. Furthermore, MET successfully controlled changes in Trimethylamine (TMA) metabolites and the overall fecal metabolite profile. MET reduces inflammation by regulating TMA lyase expression in the gut microbiota and regulating the inflammatory cascade produced by TMAO.
CONCLUSION
Our…
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