In exploring the intricate web of interconnected systems within our bodies, we often overlook the silent powerhouse known as the enteric nervous system (ENS). While the heart and blood vessels take the spotlight in discussions about cardiovascular health, the ENS quietly influences various aspects of our well-being, including the functioning of our cardiovascular system.
The ENS, often dubbed the "second brain," is a sophisticated network of neurons nestled within our gastrointestinal (GI) tract (1). Its primary role is to regulate digestion, nutrient absorption, and GI motility independently from the central nervous system. However, recent studies have shed light on the ENS's impact beyond gut-related functions (2).
Understanding the relationship between the ENS and the GI tract illuminates how disruptions in these crucial interactions—especially in the formative stages of life—can impact the development of GI disorders. Further, as the interconnected nature of the ENS becomes clearer, so too does its potential role in the functioning of distal systems such as the brain. Recent animal and translational models have implicated disrupted gut microbiota in various central nervous system (CNS) disorders, namely Parkinson’s Disease (3).
Relatedly, the vagus nerve is increasingly becoming appreciated as a crucial communicator between the gut and the heart. Playing a pivotal role in facilitating a two-way flow of information, it works as the cornerstone of the parasympathetic nervous system. With responsibilities including the regulation of fundamental bodily processes like mood, immune response, digestion, and heart rate (4), it acts as a vital bridge between the brain and the GI system, relaying information about the well-being of our internal organs to the brain through specialized nerve fibers. Any disruptions in the function of the vagus nerve can have detrimental effects such as elevating blood pressure and triggering hypertension, as well as sparking increased inflammation throughout the body. It serves as a remarkable example of the interconnectedness of our bodily systems and the profound impact it can have on our overall health and wellbeing.
The connection between the ENS and the cardiovascular system is complex. While traditionally seen as separate systems, new evidence indicates an interaction between them, suggesting communication with the microbiota in the GI tract. In addition to regulating bodily functions such as GI movement, sensation and secretion, the ENS also interacts with epithelial cells, neuroendocrine cells and immune cells to influence growth and maintain structure and function. Following this relationship, research proposes that an imbalance in gut bacteria may result in reduced heart function and increased heart muscle disease by triggering inflammation, oxidative stress and platelet activation (5).
Atherosclerosis, common cardiovascular disorder, occurs when plaque builds up in arterial walls. Recent research indicates that the gut microbiota plays a significant role in the development of atherosclerosis through pathways involving inflammation, lipid metabolism, and immune responses, all of which are influenced by the ENS (6).
Exploring the interactions between the ENS and the cardiovascular system opens up new possibilities for therapeutic interventions
Additionally, heart failure, a condition where the heart fails to effectively pump blood, is a major contributor to morbidity and mortality globally. Within this landscape, the gut-heart axis, managed by the ENS and other pathways, has become a crucial player in the progression of heart failure, with gut dysbiosis and increased intestinal permeability being key factors in disease advancement. Once considered a distant organ, the gut is now acknowledged as a substantial contributor of inflammatory stimuli, capable of affecting both the vascular endothelium and the heart by way of dysbiotic gut bacteria (7).
Exploring the interactions between the ENS and the cardiovascular system opens up new possibilities for therapeutic interventions. Recent approaches focusing on modulating the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, show promise in reducing cardiovascular risk factors and enhancing outcomes in cardiovascular diseases (8).
The enteric nervous system, often neglected in discussions regarding cardiovascular health, plays a pivotal role in the pathophysiology of various cardiovascular conditions. By delving into the intricate connections between the gut and the heart, researchers are discovering innovative therapeutic targets and strategies for preventing and treating these ailments. As our understanding deepens, tapping into the therapeutic potential of the ENS could be the key to maintaining a healthier heart and a longer life.
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Chanpong A, Borrelli O, Thapar N. Recent advances in understanding the roles of the enteric nervous system. Fac Rev. 2022 Mar 24;11:7.
Quigley EMM. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases. Curr Neurol Neurosci Rep. 2017 Oct 17;17(12):94.
Breit S, Kupferberg A, Rogler G, Hasler G. Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry. 2018 Mar 13;9:44.
Wang L, Wang S, Zhang Q, He C, Fu C, Wei Q. The role of the gut microbiota in health and cardiovascular diseases. Mol Biomed. 2022 Oct 11;3(1):30.
Shen X, Li L, Sun Z, Zang G, Zhang L, Shao C, Wang Z. Gut Microbiota and Atherosclerosis-Focusing on the Plaque Stability. Front Cardiovasc Med. 2021 Aug 3;8:668532.
Petruzziello C, Saviano A, Manetti LL, Macerola N, Ojetti V. The Role of Gut Microbiota and the Potential Effects of Probiotics in Heart Failure. Medicina (Kaunas). 2024 Feb 4;60(2):271.
Rashid S, Sado AI, Afzal MS, Ahmed A, Almaalouli B, Waheed T, Abid R, Majumder K, Kumar V, Tejwaney U, Kumar S. Role of gut microbiota in cardiovascular diseases - a comprehensive review. Ann Med Surg (Lond). 2023 Oct 18;86(3):1483-1489.