Gut Microbiota and Cardiovascular Endocrinology: Emerging Insights

The gut microbiota plays a crucial role in cardiovascular health by modulating metabolic and endocrine pathways. Given its ability to synthesize and regulate hormone-like compounds, interact with classical endocrine pathways, and influence systemic physiology, the gut microbiota functions as an endocrine organ. Recent research highlights its impact on hypertension, atherosclerosis, and heart failure through microbial metabolites, inflammation, hormonal and immune regulation. The metabolic benefits of microbial fermentation products, such as short-chain fatty acids (SCFAs), include abolishing vascular inflammation and oxidative stress, improving insulin sensitivity and lipid metabolism, and regulating blood pressure. SCFAs act on G-protein-coupled receptors (GPCRs) in endothelial and kidney cells, inhibiting angiotensin-converting enzyme (ACE) expression and reducing angiotensin II levels, thereby promoting vasodilation. Conversely, toxic microbial products including trimethylamine (TMA) and its derivative trimethylamine N-oxide (TMAO), as well as lipopolysaccharides (LPS), trigger chronic low-grade inflammation, contributing to endothelial dysfunction and atherosclerosis.



Our goal is to provide the latest updates on research uncovering previously unrecognized endocrine, paracrine, and angiocrine circuits that connect gut microbiota with various organ systems. While our primary focus is on the cardiovascular system, we also emphasize the broader role of the vasculature as a key target of microbiota-derived metabolic and endocrine regulators. By highlighting bioactive microbial metabolites as critical co-regulators alongside traditional pharmacological interventions, we aim to deepen our understanding of their production, signaling pathways, and molecular mechanisms of action. This knowledge could unlock new opportunities for innovative microbiome-based therapeutic strategies for cardiovascular and metabolic diseases, ultimately bridging the gap between microbiota research and clinical applications.

This special issue invites studies exploring the intricate connections between gut microbial communities and blood pressure regulation, including their influence on angiotensin-converting enzyme (ACE) levels, gut microbial diversity in hypertension, and microbiome-targeted antihypertensive therapies, such as specific probiotic strains and dietary supplements. We welcome research on the production of bioactive, hormone-like microbial metabolites, including short-chain fatty acids (acetate, butyrate, propionate) and tryptophan derivatives, which regulate insulin sensitivity, serotonin synthesis, blood pressure homeostasis, and inflammation. Further emphasis is placed on the signaling, epigenetic, and metabolic actions of microbial metabolites on blood and vascular cells, as well as novel metabolite-protein interactions that modulate intracellular signaling networks. This issue will also highlight advancements in personalized microbiota-based cardiovascular therapies, including the use of advanced sequencing and machine learning to identify microbiome signatures linked to cardiovascular risk. Additionally, we encourage studies on microbiome-based drug development, exploring engineered probiotics and postbiotics as precision interventions, along with investigations into diet-microbiome interactions and their impact on gut microbial composition for optimizing cardiovascular health. Finally, we seek updates on current clinical trials, studies elucidating causal relationships between microbiome alterations and cardiovascular outcomes, and multi-omics integration approaches for developing personalized treatment strategies.