Mechanisms, therapeutic implications, and methodological challenges of gut microbiota and cardiovascular diseases: a position paper by the ESC Working Group on Coronary Pathophysiology and Microcirculation. Issue 16 (14th April 2022)

• Record Type: Journal Article
• Authors: Tousoulis, Dimitris; Guzik, Tomasz; Padro, Teresa; Duncker, Dirk J; De Luca, Giuseppe; Eringa, Etto; Vavlukis, Marija; Antonopoulos, Alexios S; Katsimichas, Themistoklis; Cenko, Edina; Djordjevic-Dikic, Ana; Fleming, Ingrid; Manfrini, Olivia; Trifunovic, Danijela; Antoniades, Charalambos; Crea, Filippo
• Is Part Of: Cardiovascular research. Volume 118:Issue 16(2022)
• Page Start: 3171
• Page End: 3182
• Publication Date: 2022-04-14
• Subjects: Coronary artery disease -- Atherosclerosis -- Gut microbiota -- Trimethylamine N-oxide -- Short-chain fatty acids; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvac057
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: The human gut microbiota is the microbial ecosystem in the small and large intestines of humans. It has been naturally preserved and evolved to play an important role in the function of the gastrointestinal tract and the physiology of its host, protecting from pathogen colonization, and participating in vitamin synthesis, the functions of the immune system, as well as glucose homeostasis and lipid metabolism, among others. Mounting evidence from animal and human studies indicates that the composition and metabolic profiles of the gut microbiota are linked to the pathogenesis of cardiovascular disease, particularly arterial hypertension, atherosclerosis, and heart failure. In this review article, we provide an overview of the function of the human gut microbiota, summarize, and critically address the evidence linking compositional and functional alterations of the gut microbiota with atherosclerosis and coronary artery disease and discuss the potential of strategies for therapeutically targeting the gut microbiota through various interventions. Graphical Abstract: Graphical Abstract The pathophysiology of gut microbial associations with atherosclerosis. The figure depicts some of the key players at the organ, cellular, and molecular level, regarding the links between the gut microbiota and atherosclerosis. Diet has a profound effect on the gut microbiota, as it provides energy sources for bacterial fermentation. Undigested fibre is processed by bacteria-producing short-chain fatty acid (SCFA). Lower levels of SCFA have been linked to host inflammation, which aggravates atherosclerosis. Multiple bacterial species also produce trimethylamine (TMA) from choline, itself derived from dietary phosphatidylcholine. TMA is absorbed and metabolized to trimethylamine N-oxide in the liver and has been linked to the atherosclerotic process. Disruption of intestinal permeability may lead to bacterial lipopolysaccharide leaking into the bloodstream, initiating Toll-like receptor–mediated chronic systemic inflammation, and aggravating atherosclerosis. See text for details. Black arrows: Microbiota-related metabolites and host responses. Red arrows: Suggested proatherogenic effects.