Search Results (35)

The gut–heart axis represents a key determinant of cardiovascular (CV) system health. Emerging evidence indicates that intestinal dysbiosis can induce a state of chronic systemic inflammation which, together with mechanisms of endothelial dysfunction, increases the risk of CV diseases. Infective endocarditis (IE) exemplifies this concept, as microbiota alterations may promote bacterial translocation from the gut into the bloodstream, leading to colonization of cardiac valves and subsequent endocardial infection. This narrative review examines current scientific evidence on the relationship between the gut microbiota and CV diseases, with a particular focus on IE. We also summarize the mechanisms underlying impaired intestinal barrier integrity, immune activation, and the production of microbiota-derived metabolites that contribute to CV disease. Special attention is given to potential preventive and therapeutic strategies, including microbiota modulation, targeted antibiotic management, and personalized medicine approaches tailored to individual patient profiles. Full article

The gut microbiota is crucial for metabolic homeostasis and cardiovascular health. Dysbiosis triggers a gut–brain–heart axis dysfunction: vagal signaling promotes neuroinflammation and cerebral damage, which in turn impairs cardiac function. This bidirectional cycle is further exacerbated by reduced cerebral perfusion. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline and L-carnitine, acts as a primary mediator in this network. Elevated TMAO levels—resulting from bacterial conversion and hepatic oxidation—are linked to atherosclerosis and heart failure. Mechanistically, TMAO activates the NLRP3 inflammasome, inhibits the SIRT3-SOD2 pathway, and promotes platelet hyperreactivity. Furthermore, it modulates the autonomic nervous system, enhancing sympathetic activity and cardiac arrhythmias. Clinical evidence suggests TMAO is a potent predictor of mortality in HF. While current HF therapies focus on end-organ response (beta-blockers) or humoral pathways (ACE inhibitors), directly targeting the microbiota and TMAO offers a novel therapeutic frontier. Integrating TMAO assessment into risk models and utilizing advanced in vitro gut–brain models will be essential for developing personalized, groundbreaking cardiovascular interventions. Within this framework, the main aim of the present review is to describe how cardiac autonomic control can be directly modulated by the microbiota and its byproducts like TMAO. This latter is a leading target candidate for novel HF prevention and therapy interventions. Full article

A multifaceted clinical disease, heart failure (HF) is typified by decreased cardiac function and systemic symptoms caused by anatomical or functional abnormalities in the heart. Although traditional studies have concentrated on hemodynamic and neurohormonal processes, new data highlight the vital role that the gut microbiota and its byproducts play in the pathogenesis of HF. An imbalance in the microbial structure known as gut dysbiosis is common in HF patients and is linked to increased gut permeability, systemic inflammation, and changed bioactive metabolite synthesis. Prominent metabolites generated by the microbiota, including phenylacetylglutamine, short-chain fatty acids (SCFAs), secondary bile acids, and trimethylamine N-oxide (TMAO), have a major impact on endothelial function, cardiac remodeling, and inflammation. Together with gut-derived lipopolysaccharides, these metabolites interact with host systems to exacerbate the course of HF. Further impacting HF outcomes are comorbidities such as diabetes, obesity, and chronic renal disease, which intensify gut dysbiosis. The importance of metabolites originating from the microbiota in the progression of HF is highlighted in this review, which summarizes recent findings regarding the gut-heart axis. Additionally, it investigates how dietary changes, probiotics, prebiotics, and multi-omics techniques can all be used to improve the management of HF. This thorough analysis emphasizes the necessity of integrative therapy approaches and longitudinal research to better address the complex link between HF and the gut microbiota. Full article

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated significant cardiovascular and renal benefits beyond glycemic control, yet their integrated mechanisms remain incompletely understood. Emerging evidence highlights the gut-kidney-heart axis as a pivotal pathological network, wherein gut dysbiosis, toxic metabolite accumulation, intestinal barrier disruption, and systemic inflammation synergistically drive cardiorenal injury. This review systematically elucidates how SGLT2i modulate this axis through multi-level interventions: reshaping gut microbiota composition, enriching short-chain fatty acid-producing bacteria, suppressing trimethylamine and other toxin-generating microbes, restoring tight junction integrity, and regulating bile acid metabolism. These upstream effects reduce systemic inflammatory and metabolic stress, interrupt kidney-derived toxin amplification, and mitigate myocardial remodeling. Unlike previous reviews focusing on single-organ pathways, this work integrates microecological regulation, metabolite reprogramming, and cross-organ protection into a unified “three-axis convergence to the heart” framework. We also highlight potential species-specific microbiota regulatory profiles among different SGLT2i and propose future directions, including fecal microbiota transplantation and microbiota-targeted co-therapies, to clarify causal relationships and optimize therapeutic strategies. By positioning the gut as a modifiable upstream driver, this framework provides novel mechanistic insight and translational potential for expanding SGLT2i applications in metabolic cardiovascular disease, including in non-diabetic populations. Full article

Myocardial infarction (MI) and depression exhibit a bidirectional relationship, in which patients with MI are more susceptible to depression, and individuals with depression face a heightened risk of MI. The two diseases are intricately intertwined via the heart–brain axis. Sex, age, lifestyle, social background, comorbidities, and genetics contribute to and affect the prognosis of this combined condition. Mechanisms involving the autonomic nervous system (ANS), hypothalamic–pituitary–adrenal (HPA) axis, inflammation, thrombosis, tryptophan metabolism, renin–angiotensin–aldosterone system (RAAS), endothelial dysfunction, microRNAs, and gut microbiota, as components of the heart–brain axis, have been implicated in the pathological link between MI and depression. This review outlines the common risk factors and potential mechanisms underlying this bidirectional relationship. It treats the comorbidities of MI and depression as a unified condition, relying on evidence from clinical trials and experimental studies that directly address both diseases together rather than extrapolating from separate studies on MI or depression alone. It also discusses current therapeutic approaches, including non-pharmacological interventions like psychotherapy and exercise, and pharmacological treatments with chemical or natural compounds. Finally, this review identifies significant gaps in the pathophysiology and clinical management of MI with depression, which warrant further investigation. Full article

The human gut microbiota is a complex ecosystem that influences host metabolism, immune function, and cardiovascular health. Dysbiosis, defined as an imbalance in microbial composition or function, has been linked to the development and progression of atherosclerosis. This connection is mediated by microbial metabolites that enter the systemic circulation and interact with vascular and immune pathways. Among these, trimethylamine N-oxide (TMAO) has been most extensively studied and is consistently associated with cardiovascular events. Other metabolites, including lipopolysaccharides (LPS), short-chain fatty acids (SCFAs), and secondary bile acids, also contribute by modulating inflammation, endothelial function, and lipid metabolism. Recent research has expanded to emerging metabolites such as indoxyl sulfate, indole-3-propionic acid, and polyamines, which may provide additional mechanistic insights. These microbial products are increasingly explored as biomarkers of cardiovascular risk. TMAO has shown predictive value in large human cohorts, while microbiota composition and diversity measures remain less consistent across studies. However, interpretation of these biomarkers is limited by methodological variability, interindividual differences, and lack of standardization. Therapeutic interventions targeting the gut–heart axis are under investigation. Dietary strategies such as the Mediterranean diet and fiber-rich nutrition, probiotics and prebiotics, and fecal microbiota transplantation (FMT) show promise, while pharmacological approaches targeting TMAO or bile acid pathways are in early stages. This review summarizes current knowledge on the mechanistic, diagnostic, and therapeutic links between the gut microbiota and atherosclerosis, highlighting both established findings and emerging directions for future research. Full article

Cardiac surgery, particularly procedures involving cardiopulmonary bypass (CPB), is associated with a high risk of postoperative complications, including systemic inflammatory response syndrome (SIRS), postoperative atrial fibrillation (POAF), and infection. Growing evidence suggests that the gut–heart axis, through mechanisms involving intestinal barrier integrity and gut microbiota homeostasis, may influence these outcomes. This review summarizes the relationship between gut microbiota composition and the inflammatory response in patients undergoing cardiac surgery and the extent to which these alterations impact clinical outcomes. The reviewed studies consistently show that cardiac surgery induces notable alterations in microbial diversity and composition during the perioperative period. These changes, indicative of dysbiosis, are characterized by a reduction in health-associated bacteria such as Blautia, Faecalibacterium, and Bifidobacterium and an increase in opportunistic pathogens. Inflammatory biomarkers were frequently elevated postoperatively, even in patients without evident complications. Key microbial metabolites and biomarkers, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and bile acids (BAs), were implicated in modulating inflammation and clinical outcomes. Additionally, vitamin D deficiency emerged as a contributing factor, correlating with increased systemic inflammation and a higher incidence of POAF. The findings suggest that gut microbiota composition prior to surgery may influence the severity of the postoperative inflammatory response and that perioperative modulation of the gut microbiota could represent a novel approach to improving surgical outcomes. However, the relationship between dysbiosis and acute illness in surgical patients is confounded by factors such as antibiotic use and other perioperative interventions. Large-scale, standardized clinical studies are needed to better define these interactions and guide future therapeutic strategies in cardiac surgery. Full article

A comprehensive bibliometric analysis of literature is imperative to elucidate current research landscapes and hotspots in the interplay between gut microbiota and hypertension, identify knowledge gaps, and establish theoretical foundations for the future. We used publications retrieved from the Web of Science Core Collection (WoSCC) and SCOPUS databases (January 2001–December 2024) to analyze the annual publication trends with GraphPad Prism 9.5.1, to evaluate co-authorship, keywords clusters, and co-citation patterns with VOSviewer 1.6.20, and conducted keyword burst detection and keyword co-occurrence utilizing CiteSpace v6.4.1. We have retrieved 2485 relevant publications published over the past 24 years. A 481-fold increase in global annual publications in this field was observed. China was identified as the most productive country, while the United States demonstrated the highest research impact. For the contributor, Yang Tao (University of Toledo, USA) and the University of Florida (USA) have emerged as the most influential contributors. Among journals, the highest number of articles was published in Nutrients (n = 135), which also achieved the highest citation count (n = 5397). The emergence of novel research hotspots was indicated by high-frequency keywords, mainly “hypertensive disorders of pregnancy”, “mendelian randomization”, “gut-heart axis”, and “hepatitis B virus”. “Trimethylamine N-oxide (TMAO)” and “receptor” may represent promising new research frontiers in the gut microbiota–hypertension nexus. The current research trends are shifting from exploring the factors influencing gut microbiota and hypertension to understanding the underlying mechanisms of these factors and the potential therapeutic applications of microbial modulation for hypertension management. Full article

Heat stress has become a significant challenge in animal husbandry and human health, posing significant threats to both livestock and human health and profoundly impacting agricultural productivity. Sheng Mai San has been shown to effectively alleviate heat stress, yet the underlying mechanisms remain unclear. Therefore, this study established a heat stress model and employed Sheng Mai San as an intervention, with NAC as the positive control. Using histopathological analysis, Western blotting, ELISA, and 16S rDNA sequencing, we investigated the protective effects of Sheng Mai San against heat-stress-induced cardiac and intestinal injuries, as well as gut microbiota dysbiosis. The results demonstrated that heat stress-induced cardiac injury primarily occurred within 6–12 h of the cessation of heat stress. This injury was manifested by a significant elevation in the cardiac index, accompanied by attenuated expression of cardiac antioxidants (GSH, SOD, CAT, and T-AOC) and increased MDA content. Following Sheng Mai San intervention, the cardiac index was reduced, antioxidant indices (GSH, SOD, and CAT) were significantly elevated, and MDA and inflammatory markers (IL-1β, IL-6, and TNF-α) were markedly decreased. Additionally, Sheng Mai San was found to activate the Keap1-Nrf2 signaling pathway in the heart. Sheng Mai San demonstrated significant protective effects on small intestinal morphology, attenuating pathological alterations while promoting goblet cell proliferation. Analysis of the gut microbiota revealed that Sheng Mai San increased the Chao1, ACE, Shannon, and Simpson indices while reducing the abundance of harmful bacteria, such as g_Globicatella, g_Thermoactinomyces, g_Staphylococcus, g_Gemella, and g_Veillonella. Additionally, it promoted the expression of beneficial bacteria, including g_Lactobacillus and g_Ruminococcaceae. In summary, Sheng Mai San alleviates heat stress-induced cardiac hypertrophy and restores the oxidative stress balance in the heart. It also mitigates pathological damage in the small intestine, enhances the diversity and richness of the gut microbiota, and ameliorates gut microbiota dysbiosis. These findings highlight the significance of the heart-small intestine-gut microbiota axis in the protective effects of Sheng Mai San against heat stress injury. This study provides a potential therapeutic approach for heat-stress-related diseases and offers insights into the development of anti-heat-stress drugs. Full article

The gut microbiota has emerged as a crucial player in cardiovascular diseases, including heart failure (HF). Recent studies have highlighted the bidirectional interaction between the gut and the heart, often referred to as the gut–heart axis. Dysbiosis, characterized by alterations in microbial composition and function, has been linked to systemic inflammation, metabolic disturbances, and impaired cardiovascular homeostasis. This review explores the mechanisms through which gut microbiota influences HF, including microbial metabolite production, inflammatory pathways, endothelial dysfunction, hormonal modulation, fluid retention, and sodium absorption. The potential therapeutic implications of microbiota modulation through diet, probiotics, and pharmacological interventions are also discussed. Understanding these mechanisms could pave the way for novel diagnostic and therapeutic strategies in the management of HF. Future research should focus on longitudinal studies to establish causality and the development of personalized microbiota-based interventions. Full article

Heart failure (HF) has become an immense health concern affecting almost 1–2% of the population globally. It is a complex syndrome characterized by activation of the sympathetic nervous system and the Renin–Angiotensin–Aldosterone (RAAS) axis as well as endothelial dysfunction, oxidative stress, and inflammation. The recent literature points towards the interaction between the intestinal flora and the heart, also called the gut–heart axis. The human gastrointestinal tract is naturally inhabited by various microbes, which are distinct for each patient, regulating the functions of many organs. Alterations of the gut microbiome, a process called dysbiosis, may result in systemic diseases and have been associated with heart failure through inflammatory and autoimmune mechanisms. The disorder of intestinal permeability favors the translocation of microbes and many metabolites capable of inducing inflammation, thus further contributing to the deterioration of normal cardiac function. Besides diet modifications and exercise training, many studies have revealed possible gut microbiota targeted treatments for managing heart failure. The aim of this review is to demonstrate the impact of the inflammatory environment induced by the gut microbiome and its metabolites on heart failure and the elucidation of these novel therapeutic approaches. Full article

In this review article, we discuss and explore the role of bacteria-derived hydrogen sulfide. Hydrogen sulfide is a signaling molecule produced endogenously that plays an important role in health and disease. It is also produced by the gut microbiome. In the setting of microbial disturbances leading to disruption of intestinal homeostasis (dysbiosis), the concentration of available hydrogen sulfide can also vary leading to pathologic sequelae. The brain–gut axis is the original studied paradigm of gut microbiome and host interaction. In recent years, our understanding of microbial and host interaction has expanded greatly to include specific pathways that have branched into their own axes. These axes share a principal concept of microbiota changes, intestinal permeability, and an inflammatory response, some of which are modulated by hydrogen sulfide (H₂S). In this review, we will discuss multiple axes including the gut–immune, gut–heart, and gut–endocrine axes. We will evaluate the role of H₂S in modulation of intestinal barrier, mucosal healing in intestinal inflammation and tumor genesis. We will also explore the role of H₂S in alpha-synuclein aggregation and ischemic injury. Finally, we will discuss H₂S in the setting of metabolic syndrome as int pertains to hypertension, atherosclerosis and glucose-like peptide-1 activity. Majority of studies that evaluate hydrogen sulfide focus on endogenous production; the role of this review is to examine the lesser-known bacteria-derived source of hydrogen sulfide in the progression of diseases as it relates to these axes. Full article

Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality. Metabolomics allows for the identification of important biomarkers for CVDs, essential for early detection and risk assessment. This cross-sectional study aimed to identify novel metabolic biomarkers associated with CVDs using non-targeted metabolomics. We compared the metabolic profiles of 112 patients with confirmed CVDs diagnosis and 112 gender- and age-matched healthy controls from the Qatar Biobank database. Orthogonal partial least square discriminate analysis and linear models were used to analyze differences in the level of metabolites between the two groups. We report here a significant association between the indoleacetylglutamine pathway and cardiovascular diseases, expanding the repertoire of gut microbiota metabolites linked to CVDs. Our findings suggest that alterations in gut microbiota metabolism, potentially resulting in increased production of indoleacetate, indoleacetylglutamine, and related compounds at the expense of the cardioprotective indolepropionate, may contribute to this association. Our findings may pave the way for novel approaches in CVD risk assessment and potential therapeutic interventions targeting the gut-heart axis. Full article

The effect of the gut microbiota extends beyond their habitant place from the gastrointestinal tract to distant organs, including the cardiovascular system. Research interest in the relationship between the heart and the gut microbiota has recently been emerging. The gut microbiota secretes metabolites, including Trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids (BAs), indole propionic acid (IPA), hydrogen sulfide (H₂S), and phenylacetylglutamine (PAGln). In this review, we explore the accumulating evidence on the role of these secreted microbiota metabolites in the pathophysiology of ischemic and non-ischemic heart failure (HF) by summarizing current knowledge from clinical studies and experimental models. Elevated TMAO contributes to non-ischemic HF through TGF-ß/Smad signaling-mediated myocardial hypertrophy and fibrosis, impairments of mitochondrial energy production, DNA methylation pattern change, and intracellular calcium transport. Also, high-level TMAO can promote ischemic HF via inflammation, histone methylation-mediated vascular fibrosis, platelet hyperactivity, and thrombosis, as well as cholesterol accumulation and the activation of MAPK signaling. Reduced SCFAs upregulate Egr-1 protein, T-cell myocardial infiltration, and HDAC 5 and 6 activities, leading to non-ischemic HF, while reactive oxygen species production and the hyperactivation of caveolin-ACE axis result in ischemic HF. An altered BAs level worsens contractility, opens mitochondrial permeability transition pores inducing apoptosis, and enhances cholesterol accumulation, eventually exacerbating ischemic and non-ischemic HF. IPA, through the inhibition of nicotinamide N-methyl transferase expression and increased nicotinamide, NAD+/NADH, and SIRT3 levels, can ameliorate non-ischemic HF; meanwhile, H₂S by suppressing Nox4 expression and mitochondrial ROS production by stimulating the PI3K/AKT pathway can also protect against non-ischemic HF. Furthermore, PAGln can affect sarcomere shortening ability and myocyte contraction. This emerging field of research opens new avenues for HF therapies by restoring gut microbiota through dietary interventions, prebiotics, probiotics, or fecal microbiota transplantation and as such normalizing circulating levels of TMAO, SCFA, BAs, IPA, H₂S, and PAGln. Full article

Short-chain fatty acids (SCFAs), produced through fermentation of dietary fibers by gut bacteria, play a central role in modulating cardiovascular function and heart failure (HF) development. The progression of HF is influenced by intestinal barrier dysfunction and microbial translocation, where SCFAs serve as key mediators in the gut–heart axis. This review examines the complex metabolic interactions between SCFAs and other gut microbiota metabolites in HF, including their relationships with trimethylamine N-oxide (TMAO), aromatic amino acids (AAAs), B vitamins, and bile acids (BAs). We analyze the associations between SCFA production and clinical parameters of HF, such as left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and glomerular filtration rate (GFR). Gaining insights into metabolic networks offers new potential therapeutic targets and prognostic markers for managing heart failure, although their clinical significance needs further exploration. Full article