Pathomechanisms of Heart–Brain–Gut Axis Interactions in Cardiovascular Disease:  A Systematic Review and Evidence Mapping

Raisha Aprilia Ilman; Akina Maulidhany  Tahir; Dian Fahmi  Utami; Fadhilah  Maricar; Andi Muhammad Reis R  Saiby

doi:10.71435/742449

Authors

Raisha Aprilia Ilman Medical Profession Study Program, Faculty of Medicine, Universitas Muslim Indonesia
Akina Maulidhany Tahir Department of Cardiology, Faculty of Medicine, Universitas Muslim Indonesia
Dian Fahmi Utami Department of Psychiatry, Faculty of Medicine, Universitas Muslim Indonesia
Fadhilah Maricar Department of Cardiology, Faculty of Medicine, Universitas Muslim Indonesia
Andi Muhammad Reis R Saiby Department of Cardiology, Faculty of Medicine, Universitas Muslim Indonesia

DOI:

https://doi.org/10.71435/742449

Keywords:

Heart–Brain–Gut Axis, Gut Microbiota, Cardiovascular Disease, Systemic Inflammation, TMAO, SCFA

Abstract

Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in the world. Current scientific evidence shows that the interaction between the gut microbiota, central nervous system, and cardiovascular system known as the heart–brain–gut axis plays an important role in maintaining cardiovascular homeostasis and the development of various heart diseases. This research uses systematic review and evidence mapping methods based on PRISMA guidelines. A literature search was conducted on PubMed, ScienceDirect, Google Scholar, and ProQuest databases for articles published in 2021–2026. Articles that met inclusion criteria were extracted, narratively synthesized, and mapped to identify key mechanisms and research gaps. A total of 20 articles met the inclusion criteria, consisting of 15 literature-based articles and 5 original research articles. Evidence mapping results show that systemic inflammation is the most dominant mechanism, especially in coronary artery disease and atherosclerosis. Other important mechanisms include trimethylamine-N-oxide (TMAO), endothelial dysfunction, short-chain fatty acids (SCFA), and the autonomic nervous system. Dysbiosis of the gut microbiota contributes to cardiovascular disease through increased proinflammatory metabolites, activation of immune responses, oxidative stress, and endothelial damage. Additionally, neural pathways via the vagus nerve and hypothalamic–pituitary–adrenal (HPA) axis mediate bidirectional communication between the gut and brain that influences cardiovascular function. The heart–brain–gut axis is an integrated biological system that connects the gut microbiota, nervous system, immune system, and cardiovascular system. Systemic inflammation, TMAO, endothelial dysfunction, and microbiota dysbiosis are the main mechanisms underlying this association. Modulation of the gut microbiota has the potential to be a preventive and therapeutic strategy in the prevention and management of cardiovascular disease.

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