The Role Played by Imidazole Propionic Acid in Modulating Gut-Heart Axis and the Development of Atherosclerosis: An Explorative Review

Abstract

Recent studies have demonstrated the significant role of the normal human microbial component, also known as gut microbiome/gut microbiota (GM). Dysbiosis, or imbalance of GM, can predispose to systemic diseases, including cardiovascular disease (CVD). The GMs' influence extends further to cardiometabolic health, with microbial metabolites playing a pivotal role in these interactions. Traditional risk factors like hyperlipidemia and hypertension are now complemented by emerging evidence implicating GM-derived metabolites in the pathogenesis of atherosclerosis (ATS). Imidazole propionic acid (ImP), a metabolite of histidine derived from GM, has emerged as a significant mediator linking GM dysbiosis to ATS and CVD, or coronary artery disease (CAD). This comprehensive review synthesizes current knowledge on ImP's biosynthesis, molecular mechanisms, clinical relevance, and therapeutic potential, emphasizing its role in the gut-heart axis and cardiovascular pathology. Appropriate keywords, including "microbes", "dysbiosis", "gut microbiota/gut microbiome and cardiovascular disorders", "atherosclerosis and microbes", and "microbial metabolites", among others, were used to extract relevant studies in PubMed and Google Scholar from inception to date. ImP bridges microbial dysbiosis and CVD through endothelial dysfunction, inflammation, and metabolic disturbances. Its production is modifiable by diet and GM composition, positioning ImP as both a biomarker and therapeutic target in ATS and heart failure. Advancing understanding of ImP's biology and clinical impact will enable novel interventions to reduce the global burden of atherosclerotic cardiovascular disease (ASCVD), marking a change in basic assumptions in cardiovascular medicine centered on the gut-heart axis.

Keywords: atherosclerosis; biomarker; cardiovascular disease; coronary artery disease; dysbiosis; gut microbiome; gut microbiota; gut-heart axis; imidazole propionic acid; therapeutic target.

Figure 1. The influence of microbes on health, disease, and treatment

This image has been synthesized from references [1-21].

Figure 2. Probable mechanisms behind imidazole propionic acid induced cardiac complications

This image has been synthesized from references [23-26]. PI3K/PKB: phosphatidylinositol 3-kinase/protein kinase B; FOX01: forkhead box protein O1; VSMC: vascular smooth muscle cell; CVD: cardiovascular disease; CAD: coronary artery disease; HF: heart failure; ATS: atherosclerosis

Figure 3. Functions of gut microbiome

This image has been synthesized from references [17, 25, 40-69]. ImP: imidazole propionic acid.

Figure 4. The process of gut microbiome dysbiosis resulting in cardiovascular complications

This image has been synthesized from references [70, 71]. LPS: lipopolysaccharide; TLR4: toll-like receptor 4; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; IL-6: Interleukin-6, TNF-α: tumor necrosis factor alpha; CRP: C-reactive protein; TMAO: trimethylamine N-oxide.

Figure 5. The role played by imidazole propionic acid in the development of cardiovascular complications

This image has been synthesized from references [22-26]. FOX01: forkhead box protein O1.