Search Results (495)

Trimethylaminuria (TMAU) is a rare metabolic syndrome caused by the accumulation of trimethylamine in the body, causing odor emissions similar to rotten fish in affected patients. This condition is determined by both genetic and environmental factors, especially gut dysbiosis. The multifactorial nature of this syndrome makes for a complex and multi-level diagnosis. To date, many aspects of this disease are still unclear. Recent research revealed the FMO3 haplotypes’ role on the enzyme’s catalytic activity. This could explain why patients showing only combined polymorphisms or heterozygous causative variants also manifest the TMAU phenotype. In addition, another research hypothesized that the behavioral disturbances showed by patients may be linked to gut microbiota alterations. Our review considers current knowledge about TMAU, clarifying its molecular aspects, the therapeutic approaches used to limit this condition, and the new therapies that are under study. Full article

Biomarkers play a crucial role in various stages of disease management, including screening, diagnosis, prediction, prognosis, treatment, and safety monitoring. Although they are powerful tools in disease diagnosis, management, and drug development, identifying and validating reliable biomarkers remains a significant challenge. Among potential microbiome-derived biomarkers, trimethylamine N-oxide (TMAO) has gained notable attention for its link to atherosclerosis and cardiovascular risk. However, despite the growing body of research on TMAO, its practical application in clinical settings for disease management and patient outcome enhancement is still not a reality. This paper presents recent data on the utility of TMAO as a cardiovascular biomarker, categorized by its various roles: diagnostic, prognostic, susceptibility/risk, monitoring, pharmacodynamic/response, predictive, and safety. It also briefly discusses research on TMAO’s potential role in cardiovascular disease development. While TMAO shows promise, particularly in prognostic applications, its reliability as a biomarker has been inconsistent across studies. These variances may result from several confounding factors that affect TMAO plasma levels, including diet, kidney function, and demographic variables. The review aims to elucidate the specific contexts in which TMAO can be valuable, potentially leading to more personalized and effective management of cardiovascular disease. Full article

Myocardial infarction (MI) remains the leading cause of death globally, imposing a significant burden on healthcare systems and patients. The gut–heart axis, a bidirectional network connecting gut health to cardiovascular outcomes, has recently emerged as a critical factor in MI pathophysiology. Disruptions in this axis, including gut dysbiosis and compromised intestinal barrier integrity, lead to systemic inflammation driven by gut-derived metabolites like lipopolysaccharides (LPSs) and trimethylamine N-oxide (TMAO), both of which exacerbate MI progression. In contrast, metabolites such as short-chain fatty acids (SCFAs) from a balanced microbiota exhibit protective effects against cardiac damage. This review examines the molecular mediators of the gut–heart axis, considering the role of factors like sex-specific hormones, aging, diet, physical activity, and alcohol consumption on gut health and MI outcomes. Additionally, we highlight therapeutic approaches, including dietary interventions, personalized probiotics, and exercise regimens. Addressing the gut–heart axis holds promise for reducing MI risk and improving recovery, positioning it as a novel target in cardiovascular therapy. Full article

Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO’s aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe–TMAO pathway. Full article

Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality. Recent advancements in high-throughput omics techniques have enhanced our understanding of the human microbiome’s role in the development of CVDs. Although the relationship between the gut microbiome and CVDs has attracted considerable research attention and has been rapidly evolving in recent years, the role of the oral microbiome remains less understood, with most prior studies focusing on periodontitis-related pathogens. In this review, we summarized previously reported associations between the oral microbiome and CVD, highlighting known CVD-associated taxa such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We also discussed the interactions between the oral and gut microbes. The potential mechanisms by which the oral microbiota can influence CVD development include oral and systemic inflammation, immune responses, cytokine release, translocation of oral bacteria into the bloodstream, and the impact of microbial-related products such as microbial metabolites (e.g., short-chain fatty acids [SCFAs], trimethylamine oxide [TMAO], hydrogen sulfide [H₂S], nitric oxide [NO]) and specific toxins (e.g., lipopolysaccharide [LPS], leukotoxin [LtxA]). The processes driven by these mechanisms may contribute to atherosclerosis, endothelial dysfunction, and other cardiovascular pathologies. Integrated multi-omics methodologies, along with large-scale longitudinal population studies and intervention studies, will facilitate a deeper understanding of the metabolic and functional roles of the oral microbiome in cardiovascular health. This fundamental knowledge will support the development of targeted interventions and effective therapies to prevent or reduce the progression from cardiovascular risk to clinical CVD events. Full article

Recent advances have highlighted the gut microbiota as a significant contributor to the development and progression of atherosclerosis, which is an inflammatory cardiovascular disease (CVD) characterized by plaque buildup within arterial walls. The gut microbiota, consisting of a diverse collection of microorganisms, impacts the host’s metabolism, immune responses, and lipid processing, all of which contribute to atherosclerosis. This review explores the complex mechanisms through which gut dysbiosis promotes atherogenesis. We emphasize the potential of integrating microbiota modulation with traditional cardiovascular care, offering a holistic approach to managing atherosclerosis. Important pathways involve the translocation of inflammatory microbial components, modulation of lipid metabolism through metabolites such as trimethylamine-N-oxide (TMAO), and the production of short-chain fatty acids (SCFAs) that influence vascular health. Studies reveal distinct microbial profiles in atherosclerosis patients, with increased pathogenic bacteria (Megamonas, Veillonella, Streptococcus) and reduced anti-inflammatory genera (Bifidobacterium, Roseburia), highlighting the potential of these profiles as biomarkers and therapeutic targets. Probiotics are live microorganisms that have health benefits on the host. Prebiotics are non-digestible dietary fibers that stimulate the growth and activity of beneficial gut bacteria. Interventions targeting microbiota, such as probiotics, prebiotics, dietary modifications, and faecal microbiota transplantation (FMT), present effective approaches for restoring microbial equilibrium and justifying cardiovascular risk. Future research should focus on longitudinal, multi-omics studies to clarify causal links and refine therapeutic applications. Full article

Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. These conditions have numerous health consequences and significantly impact patients’ lifestyles. Effective long-term treatment is essential since NCDs are irreversible. Therefore, primary healthcare must be both exclusive and of the highest quality, ensuring comprehensive care. The primary goal should be to improve quality of life with a focus on patients, families, and communities, as most of these diseases can be prevented and controlled, although not cured. Several factors have been linked to individual health, including social, cultural, and economic aspects, lifestyle, and certain environmental factors, including work, that can have positive or negative effects. More of these variables may contribute to the onset of NCDs, which are defined by their chronic nature, propensity for prolongation, and generally slow rate of progression. Examples of NCDs include hypertension, type 2 diabetes (T2D), dyslipidemia, and fatty liver disease linked to metabolic dysfunction. The onset of these diseases has been associated with an imbalance in certain microbial niches, such as the gut, which hosts billions of microorganisms performing multiple metabolic functions, such as the production of metabolites like bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). Therefore, lifestyle changes and personal habits can significantly impact the gut microbiota (GM), potentially preventing chronic diseases associated with metabolism. NCDs are highly prevalent worldwide, prompting increased attention to strategies for modifying the intestinal microbiota (IM). Approaches such as probiotics, prebiotics, synbiotics, and fecal transplantation (FMT) have demonstrated improvements in the quality of life for individuals with these conditions. Additionally, lifestyle changes and the adoption of healthy habits can significantly impact IM and may help prevent chronic diseases related to metabolism. Therefore, the main aim of this review is to analyze and understand the importance of microbiota intervention in the prevention of non-communicable diseases. R3:A1 Full article

Polyvinyl alcohol (PVA)-based pH-responsive color indicators were developed using red cabbage anthocyanin (Anth) copigmented with gelatin and gallic acid (GA). The indicator prepared with gelatin and GA (GA/gelatin/Anth/PVA) was highly resistant to light exposure. GA/gelatin/Anth/PVA exhibited distinct color changes in pH 2–11 buffer solutions and stable color indication in acidic and neutral solid systems (pH 2 and 7) at 97% relative humidity. GA/gelatin/Anth/PVA exhibited the highest sensitivity to dimethylamine, followed by ammonia and trimethylamine. The addition of gelatin and GA facilitated hydrogen bonding, which enhanced thermal stability and water solubility without compromising tensile properties. A color change from purple to blue signaled spoilage when total volatile basic nitrogen values for beef and squid reached 21.0 and 37.8 mg/100 g, respectively. The GA/gelatin/Anth/PVA indicator shows potential for indicating the freshness of raw beef. Full article

Background/Objectives: This study investigated the effects of palmitoleic acid (POA) consumption on liver function, intestinal microbiota, and trimethylamine-N-oxide (TMAO) levels in the serum of mice treated with 3% L-carnitine drinking water. The purpose was to highlight the impact of POA on liver injury associated with high L-carnitine intake. Methods: A correlation analysis was carried out. The physiological and biochemical results showed that the administration of POA could alleviate liver injury induced by high L-carnitine ingestion, as reflected by a reduction in liver function indices (ALT, AST, AKP, and TBA activities) and modulation of antioxidant enzyme activities (SOD, GSH-Px, MDA, and RAHFR). The study also monitored the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Additionally, to assess the impact of POA on intestinal microbiota, we conducted a 16S rRNA high-throughput sequencing analysis. Results: The findings indicated that POA administration resulted in lower levels of TMAO in treated mice. Furthermore, POA could regulate the composition of intestinal microbiota in L-carnitine mice, particularly affecting Bacteroides vulgatus, Parabacteroides distasonis, Alistipes shahii, Lachnospiraceae NK4A136 group, and Parasutterella secunda, which were closely related to liver injury. Conclusions: In summary, POA could repair liver damage caused by high intake of L-carnitine by regulating the distribution of intestinal flora and subsequently decreasing serum TMAO levels. Full article

This study investigates the role of gut microbiota in cardiovascular diseases, with an additional focus on pro-atherogenic metabolites. We use advanced network analysis and machine learning techniques to identify key microbial features linked to coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF). This cross-sectional study included 189 participants divided into three groups: coronary artery disease (n = 93), heart failure with reduced ejection fraction (n = 43), and controls (n = 53). Assessments included physical exams, echocardiography, dietary surveys, blood analysis, and fecal analysis. Gut microbiota composition was analyzed using next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR). Statistical analysis methods for testing hypotheses and correlations, alpha and beta-diversity analyses, co-occurrence networks, and machine learning were conducted using Python libraries or R packages with multiple comparisons corrected using the Benjamini–Hochberg procedure. Significant gut microbiota alterations were observed, with higher Bacillota/Bacteroidota ratios in CAD and HFrEF groups compared to controls (p < 0.001). Significant differences were observed in α-diversity indices (Pielou, Chao1, Faith) between disease groups and controls (p < 0.001). β-diversity analyses also revealed distinct microbial profiles (p = 0.0015). Interestingly, trimethylamine N-oxide (TMAO) levels were lower in CAD and HFrEF groups compared to controls (p < 0.05), while indoxyl sulfate (IS) levels were comparable between the study groups. Co-occurrence network analysis and machine learning identified key microbial features linked to these conditions, highlighting complex interactions within the gut microbiota associated with cardiovascular disease. Full article

Differences in metabolic regulation among obesity phenotypes, specifically metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) women, may lead to varied responses to interventions, which could be elucidated through metabolomics. Therefore, this study aims to investigate the differences in metabolite profiles between MHO and MUO women and the changes following a lifestyle intervention. Serum samples from 36 MHO and 34 MUO women who participated in a lifestyle intervention for weight loss were analysed using untargeted proton nuclear magnetic resonance spectroscopy (¹H NMR) at baseline and 6 months post-intervention. Anthropometric, clinical, and dietary intake parameters were assessed at both time points. Both groups showed differential metabolite profiles at baseline and after six months. Seven metabolites, including trimethylamine-N-oxide (TMAO), arginine, ribose, aspartate, carnitine, choline, and tyrosine, significantly changed between groups post-intervention, which all showed a decreasing pattern in MHO. Significant reductions in body weight and body mass index (BMI) in the MUO correlated with changes in the carnitine and tyrosine levels. In conclusion, metabolite profiles differed significantly between MHO and MUO women before and after a lifestyle intervention. The changes in carnitine and tyrosine levels in MUO were correlated with weight loss, suggesting potential targets for therapeutic intervention. Full article

The aim of this study was to investigate the preservative properties of alga Gelidium sp. flour when included in the glazing medium employed for the frozen storage (−18 °C) of horse mackerel (Trachurus trachurus). Different concentrations (low, medium, and high) of an aqueous extract were tested and compared to a control water-glazing condition. Quality changes (lipid oxidation and hydrolysis, fatty acid (FA) profile, and trimethylamine (TMA) formation) were determined after 3- and 6-month storage periods. A general quality loss (lipid oxidation with hydrolysis development and TMA formation) with the frozen storage period was detected in all samples. The presence of an alga flour (AF) extract in the glazing medium led to a lower (p < 0.05) TBARS and fluorescent compound formation and to higher (p < 0.05) polyene values in frozen fish. Furthermore, a preserving effect on free fatty acids was detected in AF-treated fish. On the contrary, the AF-glazing treatment did not affect (p > 0.05) the TMA formation and the total n3/total n6 FA ratio. In general, preservative effects were found to be higher in frozen fish corresponding to the medium concentration tested. Current results show the potential of Gelidium sp. flour as a natural source of preservative hydrophilic compounds for the quality enhancement of frozen horse mackerel. Full article

Background/Objectives: Alterations in fecal microbial communities in patients with systemic sclerosis (SSc) are common, but the clinical significance of this observation is poorly understood. Gut microbial production of trimethylamine (TMA), and its conversion by the host to trimethylamine N-oxide (TMAO), has clinical and mechanistic links to cardiovascular and renal diseases. Direct provision of TMAO has been shown to promote fibrosis and vascular injury, hallmarks of SSc. We sought to determine levels of TMAO and related metabolites in SSc patients and investigate associations between the metabolite levels with disease features. Methods: This is an observational case:control study. Adults with SSc (n = 200) and non-SSc controls (n = 400) were matched for age, sex, indices of renal function, diabetes mellitus, and cardiovascular disease. Serum TMAO, choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine were measured using stable isotope dilution liquid chromatography tandem mass spectrometry. Results: Median TMAO concentration was higher (p = 0.020) in SSc patients (3.31 [interquartile range 2.18, 5.23] µM) relative to controls (2.85 [IQR 1.88, 4.54] µM). TMAO was highest among obese and male SSc participants compared to all other groups. Following adjustment for sex, BMI, age, race, and eGFR in a quantile regression model, elevated TMAO levels remained associated with SSc at each quantile of TMAO. Conclusions: Patients with SSc have increased circulating levels of TMAO independent of comorbidities including age, sex, renal function, diabetes mellitus, and cardiovascular disease. As a potentially modifiable factor, further studies examining the link between TMAO and SSc disease severity and course are warranted. Full article

Cardiovascular disease (CVD) may be inherited, as recently shown with the identification of single nucleotide polymorphisms (SNPs or “snips”) on a 250 kb DNA fragment that encodes 92 proteins associated with CVD. CVD is also triggered by microbial dysbiosis, microbial metabolites, metabolic disorders, and inflammatory intestinal epithelial cells (IECs). The epithelial cellular adhesion molecule (Ep-CAM) and trefoil factor 3 (TFF3) peptide keeps the gut wall intact and healthy. Variations in Ep-CAM levels are directly linked to changes in the gut microbiome. Leptin, plasminogen activator inhibitor 1 (PAI1), and alpha-1 acid glycoprotein 1 (AGP1) are associated with obesity and may be used as biomarkers. Although contactin 1 (CNTN1) is also associated with obesity and adiposity, it regulates the bacterial metabolism of tryptophan (Trp) and thus appetite. A decrease in CNTN1 may serve as an early warning of CVD. Short-chain fatty acids (SCFAs) produced by gut microbiota inhibit pro-inflammatory cytokines and damage vascular integrity. Trimethylamine N-oxide (TMAO), produced by gut microbiota, activates inflammatory Nod-like receptors (NLRs) such as Nod-like receptor protein 3 (NLRP3), which increase platelet formation. Mutations in the elastin gene (ELN) cause supra valvular aortic stenosis (SVAS), defined as the thickening of the arterial wall. Many of the genes expressed by human cells are regulated by gut microbiota. The identification of new molecular markers is crucial for the prevention of CVD and the development of new therapeutic strategies. This review summarizes the causes of CVD and identifies possible CVD markers. Full article

This research evaluated the preservative properties of flour from the alga Gelidium sp., which is a waste substrate resulting from commercial phycocolloid extraction. Gelatin-based biofilms, which included two different concentrations of red alga flour, were developed and used as packaging systems during refrigerated storage (up to 9 days at 4 °C) of Atlantic mackerel (Scomber scombrus) muscle. In all batches tested, a progressive decrease in quality could be observed in the muscle of the fish as the storage time increased. Compared with the control fish, the Gelidium alga flour extract had an inhibitory effect (p < 0.05) on microbial activity (total aerobes, psychrotrophs, and proteolytic bacteria), lipid oxidation (peroxide, thiobarbituric acid, fluorescence and polyene indices), lipid hydrolysis (formation of free fatty acids) and pH increase in refrigerated mackerel muscle. In contrast, no significant effect (p > 0.05) was observed on trimethylamine formation, Enterobacteriaceae, or lipolytic bacteria counts. A preservative effect resulting from the incorporation of Gelidium alga flour into the gelatin-based biofilm was observed, indicating both quality and safety enhancement. In accordance with current global interest in the search for natural and waste sources, a novel and beneficial use of Gelidium flour for enhancing the quality of refrigerated fish has been proposed. Full article