Search Results (408)

Obesity represents a heterogeneous metabolic disorder characterized by substantial interindividual variation in inflammatory status, insulin sensitivity, and cardiometabolic risk. Traditional anthropometric measures fail to capture this metabolic diversity, limiting risk stratification and personalized intervention strategies. This review critically examines nutritional and metabolic biomarkers that reflect the physiological dysregulation underlying obesity, including adipokines (leptin, adiponectin, resistin), inflammatory markers (C-reactive protein, interleukin-6, TNF-α), insulin resistance indices (HOMA-IR, fasting insulin, HbA1c), and lipid metabolism indicators (LDL cholesterol, triglycerides, HDL cholesterol, and liver enzymes such as ALT and GGT). Among these, elevated CRP, reduced adiponectin, and increased HOMA-IR have demonstrated the strongest clinical utility for early metabolic risk identification. We further evaluate emerging biomarkers—including circulating microRNAs, gut microbiota-derived metabolites (short-chain fatty acids, TMAO, lipopolysaccharides), and bile acid profiles—which offer additional mechanistic insight into diet–microbiome–host interactions. We systematically assess the mechanistic basis, clinical relevance, and nutritional modulation of each biomarker class, emphasizing how dietary composition—particularly fatty acid quality, fiber intake, and overall dietary patterns such as the Mediterranean diet—influences biomarker profiles and metabolic outcomes. Furthermore, we explore how biomarker-based phenotyping enables precision nutrition approaches by identifying individuals most likely to benefit from specific dietary interventions. Integration of multi-biomarker panels with clinical and genetic data holds promise for advancing from population-based dietary guidelines toward individualized nutrition strategies that optimize metabolic health and prevent obesity-related complications. Future research should prioritize validating biomarker-guided intervention frameworks, establishing standardized thresholds across diverse populations, and developing clinically implementable tools for personalized nutritional medicine. Full article

Chronic non-communicable diseases rarely occur in isolation; cardiovascular, metabolic, neurodegenerative, malignant, and age-associated disorders share upstream drivers including oxidative stress, chronic inflammation, mitochondrial dysfunction, and metabolic imbalance. This narrative review synthesizes epidemiological, interventional, and mechanistic studies identified through targeted literature searches to examine redox biology as a shared mechanistic hub linking these conditions. We evaluate antioxidant-rich dietary patterns, selected nutraceuticals, myocardial ischemia–reperfusion injury as a clinical exemplar, rare redox-imbalance disorders as mechanistic stress models, and emerging gene-based reinforcement of endogenous antioxidant systems. Rather than proposing clinical targets, we present an integrative, hypothesis-generating framework illustrating how coordinated lifestyle-driven modulation of redox balance may simultaneously influence multiple disease trajectories. Collectively, the evidence supports a unified redox framework for multi-disease prevention for multi-disease prevention and future intervention design. Full article

Prostate cancer (PCa) is one of the most common malignancies in men, and growing evidence implicates the gut microbiome as a significant, modifiable contributor to disease evolution and management. Dysbiosis influences PCa biology through effects on inflammation, immune regulation, metabolism, and hormone signaling. Microbial imbalance can promote systemic inflammation and increase intestinal permeability, activating immune signaling pathways such as NF-κB–IL-6–STAT3. In parallel, microbiome-driven metabolic effects, including IGF-1 signaling and microbial androgen synthesis or recycling, may contribute to resistance to androgen deprivation therapy (ADT). Microbial metabolites, notably short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO), exert context-dependent effects on tumor growth, treatment resistance, and progression. Conversely, beneficial microbes have been associated with improved treatment sensitivity and immune regulation. Together, these insights support the gut microbiome as a potential biomarker and emerging therapeutic target in PCa. Modulation strategies, including diet, probiotics, antibiotics, and fecal microbiota transplantation (FMT), are being explored to improve treatment response and address resistance. As mechanistic evidence continues to grow, ongoing monitoring of the gut microbiome may help inform risk stratification and treatment optimization in prostate cancer. Full article

Background and Objectives: In many neurodegenerative diseases, the pathological changes occurring in the central nervous system may be reflected in the periphery. The aim of this study was to examine the possible relationship between the retina, choroid, and nerve fibre layer thicknesses measured on optic coherence tomography (OCT) and the serum microbiota metabolite levels of trimethyl amine-N-oxide (TMAO), S-equol, Indoxyl sulphate (IS), and Maresin 1 (MaR1). Materials and Methods: This study included a total of 60 subjects, comprising 30 patients diagnosed with schizophrenia and a control group of 30 healthy individuals. A sociodemographic form was given to all the subjects and the Positive and Negative Syndrome Scale (PANSS) to the schizophrenia patients. The eye fundus was evaluated with OCT. A 5 mL blood sample was taken from the arm of each subject, and the microbiota metabolite levels of TMAO, S-equol, IS, and MaR1 were examined. Results: The retina nerve fibre layer (RNFL) analysis results showed that the RNFL superior (p = 0.016), inferior (p = 0.002), central choroid (p = 0.033), nasal choroid (p = 0.004), temporal choroid (p = 0.038), and TMAO (p = 0.001) values were significantly lower in the schizophrenia patients than in the control group. In the patient group, a significant negative correlation was determined between the RNFL temporal measurements and IS, as well as a significant positive correlation between the central choroid measurement and the nasal choroid and temporal choroid measurements and between the nasal choroid and temporal choroid measurements. A statistically significant positive correlation was seen between S-equol and TMAO. A significant negative correlation was seen between the MaR1 level and age and disease duration. Conclusions: The study results showed that fundus changes are associated with serum microbiota metabolite levels in schizophrenia patients. Therefore, these parameters may be considered potential exploratory biomarkers; however, their clinical applicability requires validation in larger longitudinal studies. Full article

Heart failure with preserved ejection fraction (HFpEF) represents the predominant form of heart failure, affecting over 50% of all heart failure patients with increasing prevalence in aging populations. Despite significant advances in cardiovascular medicine, HFpEF remains a complex clinical syndrome with poorly understood pathophysiology and limited treatment options. While most studies have traditionally focused on the renin–angiotensin–aldosterone system (RAAS) and other related mechanisms, emerging evidence has unveiled a critical bidirectional relationship between dysregulation of gut microbiota and HFpEF development. This phenomenon, mediated through microbiome-driven inflammation and endothelial dysfunction, introduces a novel concept and potential emerging conceptual framework in understanding HFpEF. This comprehensive review explores this novel gut–heart axis by synthesizing the latest evidence from original studies and clinical trials. We discuss novel mechanisms involving bacterial metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), bile acids, and amino acid derivatives. We also examine how gut dysbiosis may contribute to systemic inflammation through lipopolysaccharide translocation, NLRP3 inflammasome activation, and endothelial dysfunction. Furthermore, clinical trials investigating microbiome-targeted interventions, including probiotics, fecal microbiota transplantation, metabolite supplementation, and precision medicine approaches, are critically evaluated for their therapeutic potential. This review provides a framework for hypothesis generation and future research directions about therapeutic strategies targeting the gut–heart axis in HFpEF management. Full article

Background: Cardiovascular diseases (CVDs) are the leading global cause of mortality, with vascular calcification (VC) as a major predictor of adverse outcomes. Although vascular smooth muscle cells (VSMCs) are established contributors, the role of endothelial cells (ECs), particularly via the endothelial–mesenchymal transition (EndMT) and exosome signaling, remains less defined. Objective: This study investigated whether the gut microbiota-derived metabolite Trimethylamine-N-oxide (TMAO) induces EndMT in ECs and whether exosomes from TMAO-treated ECs regulate the VSMC phenotype and calcification. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to TMAO at physiological and pathological levels (10–50 µM). EndMT markers were analyzed by Western blotting and qPCR. Exosomes were isolated, characterized, and applied to HAVSMCs in graded doses. Osteogenic and contractile markers, β-catenin signaling, and calcification were quantified. Exosomal miR-30 and miR-222 were studied. Results: TMAO triggered dose-dependent EndMT, decreasing CD31/VE-cadherin and increasing α-SMA, N-cadherin, and vimentin. Exosomes from TMAO-treated ECs reprogrammed VSMCs, downregulating contractile proteins and upregulating RUNX2, OPN, TNAP, and β-catenin, causing calcium accumulation. These exosomes displayed elevated miR-222 and reduced miR-30, changes that activated β-catenin signaling and promoted the osteogenic reprogramming of VSMCs. Conclusions: Pathophysiological TMAO levels induce EndMT and mediate the formation of exosomes, which drive the osteogenic reprogramming and calcification of VSMCs. Full article

Background and Objectives: Cardiometabolic disease, a term encompassing metabolic syndrome (MS) and cardiovascular disease (CVD), represents a major and growing global health burden driven by interconnected metabolic and cardiovascular dysfunction. Emerging evidence suggests that the gut microbiota plays a central role in modulating metabolic, inflammatory, and cardiovascular (CV) pathways, giving rise to the concept of the heart–gut axis. However, human evidence integrating microbiome-mediated mechanisms across the cardiometabolic spectrum remains incompletely synthesized. This focused systematic review aimed to synthesize the current human evidence on microbiome-mediated mechanisms linking metabolic syndrome (MS) and related metabolic phenotypes with cardiovascular risk (CVR) and subclinical cardiovascular (CV) outcomes within the conceptual framework of the heart–gut axis. Materials and Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library in accordance with PRISMA 2020 guidelines. Human observational and interventional studies evaluating gut microbiota composition, function, or microbiota-derived metabolites in relation to cardiometabolic, and CV outcomes were included. Risk of bias was assessed using the Cochrane RoB 2 and ROBINS-I tools, and findings were synthesized narratively. Results: Ten human studies published between 2016 and 2025 met the inclusion criteria. Across these studies, gut dysbiosis was consistently associated with adverse cardiometabolic risk profiles and subclinical CV outcomes, including insulin resistance, systemic inflammation, subclinical atherosclerosis, and CV prognosis in high-risk populations. Microbiota-derived metabolites, particularly trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), as well as emerging metabolites such as phenylacetylglutamine (PAGln) and imidazole propionate (ImP), were identified as key mediators linking metabolic syndrome and related metabolic disturbances with CVR and subclinical cardiovascular disease (CVD). Markers of intestinal barrier dysfunction and endotoxemia further supported the role of chronic low-grade inflammation within the heart–gut axis. Conclusions: Current human evidence supports the heart–gut axis as a biologically plausible and clinically relevant contributor to cardiometabolic disease. Gut microbiota-derived metabolites, intestinal barrier dysfunction, and systemic inflammation represent interconnected pathways linking MS with CVR. Advancing our understanding of these mechanisms may inform the development of microbiome-targeted strategies to complement established approaches for cardiometabolic and CV prevention. Full article

Background/Objectives: Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite increasingly recognized as a pro-atherogenic factor and a biomarker of cardiometabolic risk. Dietary patterns and adiposity are key modulators of circulating TMAO levels; however, evidence on the impact of very-low-energy ketogenic therapy (VLEKT) on TMAO metabolism, particularly in women with obesity, remains limited. This study aimed to investigate the effects of VLEKT on circulating TMAO concentrations, with specific focus on treatment duration and body composition (BC) changes. Methods: This study included 43 adult women with obesity eligible for VLEKT based on meal replacements. Anthropometric measurements and BC were assessed using standardized protocols and bioelectrical impedance analysis at baseline and post-intervention. Serum TMAO concentrations were quantified by validated HPLC–ESI–MS/MS. Results: After VLEKT, participants exhibited significant reductions in body weight, BMI, waist girth, fat mass (FM), and circulating TMAO levels. Greater reductions in TMAO were observed in women with longer ketogenic exposure and more pronounced FM loss. Changes in TMAO levels correlated negatively with VLEKT duration and positively with FM variations. In multivariate models, treatment duration and FM reduction emerged as independent predictors of TMAO decrease. A Receiver Operating Characteristic (ROC) analysis identified a FM reduction ≥14.25% as the optimal threshold associated with clinically relevant TMAO lowering. Conclusions: VLEKT reduces circulating TMAO levels in women with obesity. This effect appears to be primarily driven by the duration of ketogenic exposure and the magnitude of FM loss, rather than total weight reduction alone, highlighting the relevance of BC-targeted interventions in modulating gut microbiota-derived cardiometabolic risk markers. Full article

High salinity and hardness in flowback fluids from tight reservoirs severely degrade the performance of conventional fracturing fluids, leading to formation damage and imposing major constraints on water recycling. An innovative in situ molecular interface regulation strategy that bypasses the need for costly pretreatment was proposed. A novel zwitterionic polymer was synthesized by grafting trimethylamine N-oxide (TMAO) onto hydrolyzed polyacrylamide. This hydrolyzed polyacrylamide grafted with trimethylamine N-oxide polymer (HPAMT) leverages zwitterionic TMAO groups to form a robust hydration layer approximately 0.25 nm thick on the polymer chains. Each TMAO group can immobilize up to 22.2 water molecules, effectively shielding the polymer from the detrimental effects of ions like Ca²⁺ and Na⁺, thereby preventing chain curling and preserving cross-linking sites. Experimental results demonstrate that HPAMT fracturing fluid prepared with untreated flowback fluids retains over 70% of its initial viscosity. The HPAMT fracturing fluid exhibits superior thermal and shear stability, maintaining more than 90% viscosity after exposure to 90 °C and the shear rate of 170 s⁻¹ for 60 min. Furthermore, HPAMT provides excellent proppant suspension, exceeding 60 min of static settling time. The broken gel viscosity remains below 5 mPa·s, enabling the direct reuse of flowback water. This technology overcomes the critical compatibility issue between traditional polymers and challenging brine chemistry, significantly reducing freshwater consumption and operational costs, thus presenting a viable and innovative solution for enhancing the environmental sustainability of unconventional resource development. Full article

Post-transplant diabetes mellitus (PTDM) is a common complication after liver transplantation. Trimethylamine N-oxide (TMAO), a microbiota-derived metabolite, has been linked to insulin resistance, but epidemiological findings on type 2 diabetes remain inconsistent. The Lipoprotein Insulin Resistance (LP-IR) score is a nuclear magnetic resonance (NMR)-derived marker of insulin resistance, yet its role in PTDM and interaction with TMAO are unknown. Three hundred sixty-seven (367) liver transplant recipients (LTRs) from the TransplantLines cohort were studied. Baseline TMAO and LP-IR score were quantified by NMR spectroscopy. Incident PTDM was defined by international criteria. Associations were tested using logistic regression and Cox proportional regression analysis. Effect modification was tested with interaction terms. Thirty-one out of 246 LTRs at risk developed PTDM after a median follow-up of 7.1 years. Higher TMAO (OR 2.14, p = 0.015) and LP-IR score (OR 1.66, p = 0.015) were associated with increased PTDM risk after adjustment for eGFR and immunosuppressant use. A positive interaction was present (p = 0.029) with risk amplification when both biomarkers were elevated. TMAO’s association with PTDM was strongest at high LP-IR (90th percentile; OR 3.20, p = 0.005), and LP-IR’s association was strongest at high TMAO (90th percentile; OR 2.56, p = 0.002). Time-to-event analysis confirmed these findings. The independent and positive interaction of TMAO and LP-IR with PTDM in LTRs would suggest a pro-diabetic action of TMAO that depends on insulin resistance. Full article

Background: High-fat diet-induced metabolic disorders are associated with trimethylamine (TMA)/trimethylamine N-oxide (TMAO), whose production is linked to gut microbial choline metabolism. However, changes in specific gut microbiota under a high-fat diet and the relationship between these changes and choline in TMA/TMAO production remain unclear. Methods: A total of 48 7-week-old male C57BL/6J mice were subjected to one-week acclimatization feeding, and then randomly divided into four groups (12 mice per group) to establish a 2 × 2 factorial design animal experiment: the control group (CON, basal diet), the choline-supplemented control group (CON + C, basal diet supplemented with 1% choline), the high-fat diet group (HF, high-fat diet), and the high-fat plus choline group (HF + C, high-fat diet supplemented with 1% choline). The experiment lasted for 9 weeks, during which dynamic monitoring of TMAO levels in mice was performed in the first 4 weeks. At the ninth week, the mice were sacrificed and samples were collected for subsequent assays, including the concentrations of TMA and TMAO in serum, colonic contents and feces; the pathological morphology of liver tissue, adipocyte staining characteristics and serum biochemical parameters; and the expression levels of key genes and proteins in liver, small intestine and colon tissues. Meanwhile, metagenomic analysis was conducted on colonic contents, combined with machine learning to predict the correlation between gut microbiota and TMA. In addition, gene cloning, multiple sequence alignment, molecular simulation and in vitro culture experiments were carried out to verify the TMA-producing function of the target strain. Results: This study elucidated that high-fat diet and high choline exert a significant interaction in TMA/TMAO production through a 2 × 2 animal experiment; meanwhile, the significantly increased TMA/TMAO levels co-induced by the two factors further exacerbate metabolic disorders. Notably, through combined metagenomics and machine learning, we identified Serratia marcescens as the primary TMA-producing microorganism under high-fat/choline diet induction. In vitro cultures simulating the intestinal environment revealed that the TMA conversion ability of Serratia marcescens is time-dependent, reaching 60 ± 2.49% after 24 h of anaerobic culture with choline chloride. Multiple sequence alignment and molecular simulation further demonstrated that the CutC enzyme of Serratia marcescens has a conserved amino acid sequence and high affinity for choline. Conclusions: We uncovered a two-factor synergistic effect of a high-fat/choline diet on TMA/TMAO, and for the first time identified the genus Serratia as a TMA-producing bacterium. These findings provide a new potential target for intervening in metabolic disorders mediated by high-fat diet-induced TMAO elevation. Full article

Background: The heart depends on a continuous and flexible energy supply from fatty acids, glucose, and other substrates. Emerging evidence shows that gut microbiota-derived metabolites—such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), secondary bile acids, indoles, phenylacetylglutamine (PAGln), and branched-chain amino acids—modulate cardiac metabolism and function. Although clinical evidence linking these metabolites to cardiovascular outcomes is expanding, most data remain associative, with limited causal or interventional proof. Methods: A comprehensive narrative review was conducted (PubMed 2010–2025) to integrate preclinical, clinical, and Mendelian randomization studies on microbiota-derived metabolites and cardiovascular disease, complemented by evidence from dietary and interventional trials. Results: Gut-derived metabolites regulate mitochondrial energetics, inflammatory, immune system, and oxidative pathways, and endothelial and platelet activation. Elevated plasma TMAO and PAGln levels are often associated with adverse cardiovascular outcomes, while SCFAs and indole derivatives may related to protective effects. However, findings across cohorts remain heterogeneous, largely due to differences in diet, renal function, and analytical methods. Dietary patterns rich in fiber and plant-based nutrients favor beneficial metabolite profiles, underscoring the nutritional modulation of the gut–heart axis. Conclusions: The diet–microbiota–metabolite axis represents an emerging pathway connecting nutrition to cardiovascular health. Translating this knowledge into prevention and therapy will require large-scale randomized studies and integrated multi-omics approaches. Dietary modulation of microbial metabolism may ultimately become a novel strategy for cardiometabolic protection. Full article

Neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) share key molecular features, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and progressive neuronal loss. Increasing evidence indicates that gut dysbiosis and alterations in microbiota-derived metabolites are involved in these processes through multiple pathways along the gut–brain axis. However, while broad compositional changes are well-documented, a critical knowledge gap remains regarding the specific biochemical signal transduction pathways translating dysbiosis into pathology. This narrative review addresses this gap by synthesizing current human and experimental studies addressing gut microbiota alterations in AD, PD, and ALS, with particular emphasis on the biochemical and molecular mechanisms mediated by gut-derived metabolites. Dysbiosis in neurodegenerative diseases is frequently associated with reduced abundance of short-chain fatty acid (SCFA)-producing bacteria and altered metabolism of SCFAs, bile acids, tryptophan-derived indoles, trimethylamine-N-oxide (TMAO), and lipopolysaccharides (LPS). These microbial metabolites have been shown to modulate intestinal and blood–brain barrier integrity, influence Toll-like receptor- and G protein-coupled receptor-dependent signaling, regulate microglial activation, and affect molecular pathways related to protein aggregation in experimental models. In addition, emerging evidence highlights the involvement of oxidative and nitrosative stress, immune–metabolic crosstalk, and altered xenobiotic metabolism in microbiota–host interactions during neurodegeneration. By integrating microbiological, metabolic, and molecular perspectives, this review underscores the important and emerging role of microbiota-derived molecules in neurodegenerative disorders and outlines key chemical and metabolic pathways that may represent targets for future mechanistic studies and therapeutic strategies. Full article

Vascular calcification (VC) is a pathological process involving the deposition of mineral salts within the vascular wall, representing a significant risk factor for the development and progression of cardiovascular disease. The gut microbiota refers to the diverse microbial ecosystem inhabiting the gastrointestinal tract, including bacteria, fungi, viruses, and other microorganisms. This community exhibits considerable variability in both population density and taxonomic composition, with current estimates indicating approximately 10¹³–10¹⁴ microorganisms residing in the human gut. Recent studies suggest that metabolites produced by the gut microbiota may influence the pathogenesis of VC through the gut–vascular axis. This review consolidates current findings on the molecular mechanisms driving VC and examines the potential contribution of gut microbiota dysbiosis to vascular pathology. Particular attention is given to the functional roles of microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), lipopolysaccharide (LPS), uremic toxins, secondary bile acids, and vitamin K in modulating calcific processes. In addition, current limitations in the existing literature are outlined, and potential therapeutic approaches, including probiotic use, prebiotic interventions, and targeted dietary strategies, are discussed in the context of their relevance for future clinical management of VC. Full article

Objective: The study aims to evaluate the diagnostic and prognostic efficacy of gut-derived trimethylamine N-oxide (TMAO) as a molecular biomarker for heart failure (HF) in comparison to the N-terminal pro-B-type natriuretic peptide. Background: The clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) is frequently affected by non-cardiac physiological variables, including adiposity, advanced age, and renal clearance rates. Consequently, there is a compelling need for additional biomarkers. This analysis investigates TMAO as a critical mediator within the gut–heart axis, reflecting systemic inflammation and myocardial fibrosis secondary to intestinal dysbiosis. Methods: A comprehensive literature search was conducted using PubMed. Keywords such as “trimethylamine N-oxide”, “heart failure”, “heart failure with preserved ejection fraction” and “N-terminal pro-B-type natriuretic peptide” were used. The inclusion criteria comprised original research and literature reviews describing the pathophysiological mechanisms and clinical utility of TMAO in the context of HF diagnosis and prognosis. Results: The analyzed literature suggests that TMAO functions as an independent predictor of major adverse cardiovascular events, correlating with all-cause mortality and rehospitalization risk across all HF phenotypes. Furthermore, data indicate that using TMAO alongside NT-proBNP measurements may predict patient risk more accurately, particularly in patients where natriuretic peptide interpretation is traditionally obscured by comorbidities such as diabetes mellitus and chronic kidney disease. Conclusions: Although NT-proBNP remains the gold standard for acute diagnosis, TMAO provides significant value for long-term clinical management. By serving as a metabolic–inflammatory indicator, TMAO complements standard diagnostic panels, offering deeper insights into the prognostic trajectory and the underlying intestinal barrier integrity of patients with HF. Full article