Gut Molecules in Cardiometabolic Diseases: The Mechanisms behind the Story

Abstract

Atherosclerotic cardiovascular disease is the most common cause of morbidity and mortality worldwide. Diabetes mellitus increases cardiovascular risk. Heart failure and atrial fibrillation are associated comorbidities that share the main cardiovascular risk factors. The use of incretin-based therapies promoted the idea that activation of alternative signaling pathways is effective in reducing the risk of atherosclerosis and heart failure. Gut-derived molecules, gut hormones, and gut microbiota metabolites showed both positive and detrimental effects in cardiometabolic disorders. Although inflammation plays a key role in cardiometabolic disorders, additional intracellular signaling pathways are involved and could explain the observed effects. Revealing the involved molecular mechanisms could provide novel therapeutic strategies and a better understanding of the relationship between the gut, metabolic syndrome, and cardiovascular diseases.

Epigenetics of Early Cardiometabolic Disease: Mechanisms and Precision Medicine

“…The gut microbiome has been implicated in the development and progression of CVD through various poorly understood mechanisms, including modulation of host metabolism, inflammation, and immune function. [46][47][48] Bacterial epigenomics (ie, DNA methylation, posttranslational modifications of histone-like proteins, and noncoding RNA) have been shown to play critical roles in bacterial virulence, metabolism, and adaptation to the host environment in bacteria 49 ; however, until recently, a significant challenge on the progress of this research has been the lack of efficient and straightforward methods for comprehensive genomic methylome profiling in bacteria. 50 Nevertheless, there is a growing interest in gut bacterial epigenomics as a promising area of research for understanding the mechanisms underlying the gut microbiome's contribution to CVD.…”