Trimethylamine N-oxide Research Articles

Discovery of Noninvasive Biomarkers for Radiation Exposure via LC-MS-Based Hair Metabolomics.

Ionizing radiation exposure from a potential nuclear energy plant leak or detonation of a nuclear weapon can cause massive casualties to both warfighters and civilians. RNA, proteins, and metabolite biomarkers in biological specimens like blood and tissue have shown potential to determine radiation dose levels. However, these biomarkers in blood and urine are short-lived, typically detectable within hours or a few days. To address the need for stable, long-term radiation exposure biomarkers, we developed two mass spectrometry-based methods using noninvasive hair samples to identify radiation-exposure biomarkers. Our results show that hippuric acid and 5-methoxy-3-indoleacetate significantly increase after higher (4 gray) doses of gamma irradiation compared to lower (1 and 2 Gy) doses or nonexposed hair samples. While 2-aminooctadec-4-ene-1,3-diol, oleoyl ethanolamide, palmitoylcarnitine, 25-hydroxy vitamin D3, vernolic acid, and azelaic acid significantly increased over time after exposure. Trimethylamine N-oxide (TMAO) was found in higher concentrations in female specimens across all time points. Further validation using a machine learning model suggested that these biomarkers can predict differences in the exposure dose and time point. Our findings highlight the potential of noninvasive hair sample analysis for assessing radiation exposure, offering a viable alternative to address critical public health concerns of unexpected radiation exposure.

Short-Chain Fatty Acids and Their Metabolic Interactions in Heart Failure

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.

Deodorization mechanism of the main aroma compounds on the fishy odor in boiled fish during heating.

A boiled fish simulation system was constructed to explore the deodorization effect of main aroma compounds (MAC) on myofibrillar protein (MP) with main fishy compounds (MFC) during heating. The results showed that the MFC content of boiled fish was reduced by 63.10-78.10% when boiled by heat-stable emulsions loading MAC. Specifically, adding linalool, anethole, and myrcene significantly elevated the free percentage of hexanal, heptanal, and 1-octen-3-ol after heating, while the free percentage of octanal and nonanal markedly increased by adding anethole and limonene. Molecular docking exhibited that MAC and MFC possessed co-binding sites with myosin. Linalool and anethole were competitively bound to MP through hydrophobic and hydrogen bonding sites, while myrcene and limonene were via hydrophobic interaction sites. Moreover, MAC-MP formed a relatively stable structure, exhibiting increased α-helix content and decreased surface hydrophobicity, which reduced the available sites for MFC binding, ultimately desorbed MFC (65.46%-95.89%).

Abstract WP336: Elevated Trimethylamine N-Oxide Levels Are Associated with Ischemic Stroke and Hypertensive Intracerebral Hemorrhage

Abstract WP336: Elevated Trimethylamine N-Oxide Levels Are Associated with Ischemic Stroke and Hypertensive Intracerebral Hemorrhage

Trimethylamine N-Oxide (TMAO) and TNF-α Levels in Periodontal Disease Associated With Smoking.

Trimethylamine N-oxide (TMAO) is a compound involved in the pathogenesis of various systemic inflammatory diseases, including cardiovascular conditions. The aim of this study was to determine differences in saliva and serum levels of TMAO between periodontitis and healthy patients according to smoking status. The study included four systemically healthy groups: periodontally healthy non-smokers (NS-Control; n = 25), non-smokers with Stage-III-Grade-B periodontitis (NS-Periodontitis; n = 25), periodontally healthy smokers (S-Control; n = 25), and smokers with Stage-III Grade-C periodontitis (S-Periodontitis; n = 25). Periodontal parameters were recorded. TMAO levels were determined in saliva and serum samples using liquid chromatography-mass spectrometry (LC-MS/MS). TNF-α levels were measured by the ELISA method. Salivary TNF-α and TMAO levels were significantly elevated in the smoking periodontitis group compared to other groups (p < 0.001 and p = 0.003, respectively). Serum TMAO levels were also significantly higher in the smoking periodontitis group compared to non-smoking controls and non-smoking periodontitis. TMAO/SFR ratios were notably higher in the smoking periodontitis group compared to other groups, and a strong positive correlation was observed between salivary TMAO and TNF-α levels (r = 0.892, p < 0.001). The data suggested that TMAO and TNF-α are associated with inflammatory mechanisms of periodontitis in cases where periodontitis coexists with smoking. NCT06580431.

The Crucial Role of Gut Microbiome in Cardiovascular Health

Madam, The intestinal microbiome refers to the vast assortment of tiny organisms in the human digestive tract. These bacteria support the body's physiological processes and biochemical responses via the compounds they generate. Research suggests that variations in gut microbiota may influence a variety of human health disorders, notably those involving the heart. Recent studies have shown that changes in the types and activities of bacteria in the intestines, known as gut microflora dysbiosis, can hasten the course of cardiovascular illnesses 1. Another research also tied gut microbiota to heart disease, but this time by demonstrating how metabolites like trimethylamine N-oxide (TMAO) will increase risk, indicating that dietary and probiotic strategies could be used for remedy 2. A recent study from April 2024 identified Oscillibacter and Eubacterium as synergistic cholesterol metabolisers. The intermediate products that these bacteria form while converting cholesterol are finally degraded by other bacteria and flushed out from the body, reducing gut cholesterol and modulating the host's biochemical pathways, hence reducing both faecal and plasma cholesterol levels. The results may serve to facilitate novel potential interventions, for example targeting the microbiome in cardiovascular disease (CVD) treatment 3. A novel association was observed that higher serum C-reactive protein (CRP) levels correlate with Parabacteroides merdae and unclassified Firmicutes strongly associate with plasma cholesterol. As for Firmicutes a well-defined metagenomic species pangenome (MSP) from this phylum, termed msp_120, was found to be associated with higher cholesterol levels that indicate its role in cholesterol metabolism and thus possibly also as a determinant of cardiovascular disease risk factors concerning high serum-cholesterol level. This finding reveals a beholden link between the gut microbiome and systemic inflammation with CVD 3. In Pakistan, where CVDs are a major health concern, there is a significant research gap regarding the local gut microbiome's role in CVD. We conducted thorough research on PubMed and found no original research articles studying the relationship of gut microbiome with CVD except for a few review articles 4 and 5; this is indicative of the lack of attention to this topic in Pakistan. It is important to perform ethnic-specific studies for these unique interactions in the Pakistani population. Research in this direction may point out the specific role of gut microbiota so probiotic interventions and dietary recommendations can be used to improve cardiovascular health in the Pakistani population.

Effects of Dietary Fiber Supplementation on Modulating Uremic Toxins and Inflammation in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Emerging evidence supports the beneficial effects of dietary fiber supplementation in alleviating gut dysbiosis, which leads to a reduction in uremic toxins and inflammatory markers in chronic kidney disease (CKD) patients. However, current evidence-based renal nutrition guidelines do not provide recommendations regarding dietary fiber intake. We performed a systematic review and meta-analysis to investigate and highlight the effects of dietary fiber supplementation on modulating uremic toxins and inflammatory markers in individuals with CKD, with or without dialysis. The eligible randomized controlled trials (RCTs) were identified from PubMed, Scopus, and Cochrane Central Register of Controlled trials until 27 November 2024. The results were synthesized using a random-effects model and presented as standardized mean differences (SMDs) with a 95% confidence interval (CI). A total of 21 studies with 700 patients were included. When compared with the control group, dietary fiber supplementation ranging from 6 to 50 g/day, for typically more than 4 weeks, could significantly reduce the levels of serum uremic toxins, including p-cresyl sulfate, indoxyl sulfate, and blood urea nitrogen (SMD −0.22, −0.34, −0.25, respectively, with p-values &lt; 0.05), as well as biomarkers of inflammation, including interleukin-6 and tumor necrosis factor alpha (SMD −0.44, −0.34, respectively, with p-values &lt; 0.05). These beneficial effects were consistent across different types of fibers and CKD status (with or without dialysis). However, no significant reduction in serum trimethylamine N-oxide, uric acid, and high-sensitivity C-reactive protein levels was observed with dietary fiber intervention. This study would pave the way for prioritizing dietary quality, particularly a fiber-rich diet, beyond the traditional focus on the quantities of protein, energy, and electrolyte restrictions among individuals with CKD.

Interaction studies unveil potential binding sites on bovine serum albumin for gut metabolite trimethylamine n-oxide (TMAO)

Trimethylamine-N-oxide (TMAO) is gut microbiota-derived metabolite, plays a critical role in human health and diseases such as metabolic, cardiovascular, colorectal cancer and, neurological disorders. Binding interactions between TMAO and serum albumins are crucial to understand the impact of TMAO on disease mechanisms. However, detailed insights into the interaction mechanisms, preferred binding locations, and conformational changes in BSA upon binding TMAO are still unclear. TMAO interacts with serum albumin in human body and thus, a model study of interaction for TMAO-BSA conjugate is presented in support of it. Decrease in absorbance intensity of protein upon interaction with metabolites reveals conjugate formation, while fluorescence spectroscopy indicate static quenching. Contact angle measurements further reveal the hydrophilic nature of the TMAO-BSA complex, while CD and FTIR support conformational changes in BSA upon binding but structure remain intact. Computational studies, such as molecular docking, molecular dynamics simulation and, MM/GBSA, confirm a stable complex with a binding energy of − 3.6 kcal/mol. These findings provide a foundation for understanding the pharmacodynamics and pharmacokinetics of TMAO and may aid in developing strategies for treating diseases, such as chronic kidney disease and neurological disorder where TMAO-serum albumins interaction are implicated.

Exploring the Potential of Stem Cells in Modulating Gut Microbiota and Managing Hypertension.

Hypertension, commonly known as high blood pressure, is a significant health issue that increases the risk of cardiovascular diseases, stroke, and renal failure. This condition broadly encompasses both primary and secondary forms. Despite extensive research, the underlying mechanisms of systemic arterial hypertension-particularly primary hypertension, which has no identifiable cause and is affected by genetic and lifestyle agents-remain complex and not fully understood. Recent studies indicate that an imbalance in gut microbiota, referred to as dysbiosis, may promote hypertension, affecting blood pressure regulation through metabolites such as short-chain fatty acids and trimethylamine N-oxide. Current antihypertensive medications face limitations, including resistance and adherence issues, highlighting the need for novel therapeutic approaches. Stem cell therapy, an emerging field in regenerative medicine, shows promise in addressing these challenges. Stem cells, with mesenchymal stem cells being a prime example, have regenerative, anti-inflammatory, and immunomodulatory properties. Emerging research indicates that stem cells can modulate gut microbiota, reduce inflammation, and improve vascular health, potentially aiding in blood pressure management. Research has shown the positive impact of stem cells on gut microbiota in various disorders, suggesting their potential therapeutic role in treating hypertension. This review synthesizes the recent studies on the complex interactions between gut microbiota, stem cells, and systemic arterial hypertension. By offering a thorough analysis of the current literature, it highlights key insights, uncovers critical gaps, and identifies emerging trends that will inform and guide future investigations in this rapidly advancing field.

Impact of Monascus purpureus combined with Lactobacillus plantarum and Saccharomyces cerevisiae fermentation on nutritional and flavor characteristics of Pyropia yezoensis.

Fermentation can promote various properties of food. This study investigated the impact of fermentation by Monascus purpureus combined with Lactobacillus plantarum and Saccharomyces cerevisiae on the physicochemical and flavor characteristics of Pyropia yezoensis. Results indicate that the protein and free amino acid content increased threefold. A total of 62 volatile flavor compounds were identified by GC-IMS. Alcohols, ketones and esters were enhanced with 2- to 6-fold, while aldehydes were reduced by 76.56%, contributing to the enhancement of pleasant fragrances and the reduction of fishy and seawater odors. As for the non-volatile properties, the content of organic acids and free amino acids increased from 2.18mg/g and 0.19mg/g to 46.03mg/g and 4.93mg/g, respectively, as assessed by HPLC and amino acid analyzer. The metabolic pathways of non-volatile substances were speculated upon. This work provides a basic theory and a practical reference for fermentation food processing of P. yezoensis.

The effect of high-fiber diet based on gut microbiota in patients with chronic heart failure.

Objective: This research explored the effect of high-fiber diet based on gut microbiota on chronic heart failure (HF) patients. Methods: Chronic HF patients, who had undergone a dietary survey indicating a daily dietary fiber intake of less than 15g/d were divided into the control and study groups (n = 50). In addition to conventional heart failure treatment, the study group received dietary guidance, while the control group did not receive any dietary guidance and maintained their usual low-fiber dietary habits. After one year intervention, the daily dietary fiber intake, abundance of gut microbiota, plasma trimethylamine N-oxide (TMAO), albumin (ALB), prealbumin (PA), transferrin (TF), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), left ventricular ejection fraction (LVEF), left ventricular end-diastolic index (LVEDVI), and left ventricular end-systolic volume index (LVESVI), Barthel index (BI), and 6 min walking distance (6 MWD) were compared. Results: After intervention, in both groups, the daily dietary fiber intake increased, abundance of Firmicutes, Proteobacteria, Actinobacteria, Fusobacteria decreased and that of Bacteroides increased; the plasma TMAO decreased; serum ALB, PA, and TF levels increased; serum CRP, TNF-α, IL-6, and IL-8 levels decreased, and the change was greater in the study group; LVEF elevated, LVEDVI and LVESVI reduced, and the differences between both groups were not significant; BI and 6 MWD elevated, and the study group was higher than the control group. Conclusion: High-fiber diet positively regulates the composition of gut microbiota, nutritional status and microinflammatory level in chronic HF patients, thereby improving patients' quality of life.

Feasibility of detecting non-small cell lung cancer using exhaled breath condensate metabolomics.

Lung cancer is one of the most common malignancy in the world, and early detection of lung cancer remains a challenge. The exhaled breath condensate (EBC) from lung and trachea can be collected totally noninvasively. In this study, our aim is to identify differential metabolites between non-small cell lung cancer (NSCLC) and control EBC samples and discriminate NSCLC group from control group by orthogonal projections to latent structures-discriminant analysis (OPLS-DA) models. The EBC differential metabolites between NSCLC patients (n = 29) and controls (n = 24) (20 healthy and 4 benign individuals) were identified using ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS)-based untargeted metabolomics method. The upregulated metabolites in EBC of NSCLC included amino acids and derivatives (phenylalanine, tryptophan, 1-carboxyethylisoleucine/1-carboxyethylleucine, and 2-octenoylglycine), dipeptides (leucyl-phenylalanine, leucyl-leucine, leucyl-histidine/isoleucyl-histidine, and prolyl-valine), and fatty acids (tridecenoic acid, hexadecadienoic acid, tetradecadienoic acid, 9,12,13-trihydroxyoctadec-10-enoic acid/9,10,13-trihydroxyoctadec-11-enoic acid (9,12,13-TriHOME/9,10,13-TriHOME), 3-hydroxysebacic acid/2-hydroxydecanedioic acid, 9-oxooctadeca-10,12-dienoic acid/9,10-Epoxy-12,15-octadecadienoate (9-oxoODE/9(10)-EpODE), and suberic acid). The downregulated metabolites in EBC of NSCLC were 3,4-methylenesebacic acid, 2-isopropylmalic acid/3-isopropylmalic acid/2,3-dimethyl-3-hydroxyglutaric acid, and trimethylamine-N-oxide (TMAO). The OPLS-DA model based on 5 EBC metabolites achieved 86.2% sensitivity, 83.3% specificity and 84.9% accuracy, showing a potential to distinguish NSCLC patients from controls.

Impact of the Healthy Lifestyle Community Program (HLCP-3) on Trimethylamine N-Oxide (TMAO) and Risk Profile Parameters Related to Lifestyle Diseases During the Six Months Following an Intervention Study.

The dietary components choline, betaine, and L-carnitine are converted by intestinal microbiota into the molecule trimethylamine (TMA). In the human liver, hepatic flavin-containing monooxygenase 3 oxidizes TMA to trimethylamine-N-oxide (TMAO). TMAO is considered a candidate marker for the risk of cardiovascular disease. The Healthy Lifestyle Community Program cohort 3 (HLCP-3) intervention was conducted with participants recruited from the general population in Germany (intervention: n = 99; control: n = 48). The intervention included intensive educational workshops, seminars, and coaching activities. The assessment was conducted using a complete case analysis (CCA) of the participants. The intervention was carried out for a ten-week intensive phase and an alumni phase. The interventional program emphasizes adopting a healthy plant-based diet and reducing meat consumption, as adherence to such a diet may lead to lowering TMAO levels. Additionally, it provides general recommendations about physical activity, stress management, and community support. The control group did not receive any intervention. TMAO was evaluated using stable isotope dilution liquid chromatography, and tandem mass spectrometry was used to measure fasting plasma levels of TMAO. The present study aimed to determine the impact of the Healthy Lifestyle Community Program (HLCP-3) on risk profiles for lifestyle-related diseases and TMAO plasma levels. Significant decreases in most risk profile parameters were detected, and a non-significant decrease in plasma TMAO levels was observed in the intervention group (0.37 (-1.33; 0.59) µmol/L). Furthermore, for the intervention group, after a six-month follow-up period, there was a significant negative correlation between higher healthy plant diet index (hPDI) scores and a decrease in plasma TMAO (ß = -0.200, p = 0.027). Additionally, a significant negative correlation was observed between the TMAO level and the scores for adherence to the plant diet index (PDI) (r = -0.195; p = 0.023). HLCP-3 is effective at improving adherence to a plant-based diet and improving risk profile parameters. However, long-term interventions involving stricter dietary programs in the sense of a plant-based diet are recommended if significant decreases in TMAO levels are to be obtained.

Circulating serum metabolites as biomarkers and predictors of residual feed intake in lactating dairy cows

This study explored the potential of circulatory serum metabolite profiles to increase understanding of the physiology of feed efficiency and identify biomarkers to predict residual feed intake (RFI) in lactating Holsteins. Serum metabolite profiles were compared in high (n = 20) and low RFI (n = 20) cows at early, mid, and late lactation stages. The low RFI cows had decreased (P < 0.05) concentrations of dodecanoylcarnitine, dodecenoylcarnitine, dodecanedioylcarnitine, tetradecanoylcarnitine, succinic acid, trimethylamine N-oxide, betaine, and increased concentrations of p-Hydroxyhippuric acid, hydroxysphingomyeline C16:1, phosphatidylcholine diacyl C40:6, and glutarylcarnitine at early lactation. A similar comparison at mid lactation stage showed altered serum concentrations of 26 metabolites that fall into the categories of acyl carnitines, glycerophospholipids, biogenic amines, amino acids, and organic acids. At late lactation, fewer sets of metabolites were significantly affected by RFI grouping. Receiver operator curve analyses identified p-Hydroxyhippuric acid as the top biomarker at early lactation and acetylornithine at mid and late lactation. Models based on sets of serum metabolites in early, mid, and late lactation stages predicted RFI with a validation coefficient of determination of 0.54, 0.68, and 0.64, respectively. This study demonstrated the potential of circulatory serum metabolites as biomarkers and predictors of RFI in lactating dairy cows.

A scoping review evaluating the current state of gut microbiota and its metabolites in valvular heart disease physiopathology.

The human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored. Peer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included. Eligible studies used 16S rRNA or shotgun sequencing, metabolite profiling by mass spectrometry, and examined osteogenesis or fibrosis signalling in valve cells. Methods and findings were qualitatively analysed, with data charted to summarize study design, materials and outcomes. Thirteen studies were included in the review: five human, three animal and five invitro. Of the nine studies on calcific aortic stenosis (CAS), elevated trimethylamine N-oxide (TMAO) levels were linked to an increased risk of cardiovascular events in cohort studies, with CAS patients showing higher levels of Bacteroides plebeius, Enterobacteriaceae, Veillonella dispar and Prevotella copri. Invivo, TMAO promoted aortic valve fibrosis, while tryptophan derivatives stimulated osteogenic differentiation and interleukin-6 secretion in valvular interstitial cells. Two studies on rheumatic mitral valve disease found altered microbiota profiles and lower short-chain fatty acid levels, suggesting potential impacts on immune regulation. Two studies on Barlow's mitral valve disease in animal models revealed elevated TMAO levels in dogs with congestive heart failure, reduced Paraprevotellaceae, increased Actinomycetaceae and dysbiosis involving Turicibacter and E. coli. TMAO has been mainly identified as a prognostic marker in VHD. Gut microbiota dysbiosis has been observed in various forms of VHD and deserve further study.

Design and Optimization of a Two-Component TorRST-Based Biosensor for Detection and Degradation of Trimethylamine N-Oxide.

In mammals, Trimethylamine N-oxide (TMAO) is involved in various physiological processes, and is considered a biomarker for multiple diseases. As a natural molecule found in marine organisms, TMAO is also an important indicator of seafood freshness. In this study, a TMAO biosensor was developed in Escherichia coli harnessing TorRST two-component system. By using a cascade amplification circuit based on HrpRS-PhrpL, the biosensor's dynamic range was increased from 4.1- to 10.3-fold. By optimizing the affinity between the regulatory protein TorR and DNA binding sites in promoters, the concentration for 50% of maximal effect (EC50) value was reduced from 1008 to 141 μM. The biosensor was successfully used for aquatic sample detection. By introducing an exogenous TMAO degradation pathway into E. coli Nissle 1917, a probiotic chassis capable of TMAO detection, transportation, and degradation was constructed, providing an effective tool for rapid detection of TMAO and prevention of multiple diseases.

Gut microbiome dysbiosis is not associated with portal vein thrombosis in patients with end-stage liver disease: a cross-sectional study.

Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in ESLD patients is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a pro-inflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development. We investigated whether gut microbiome diversity, bacterial species, metabolic pathways, and TMAO levels are associated with PVT in ESLD patients. Fecal samples, plasma samples and data from ESLD patients and healthy controls were collected through the TransplantLines Biobank and Cohort Study. PVT was defined as a thrombus in the portal vein within a year prior to or after fecal sample collection. Fecal samples were analyzed using Shotgun Metagenomic Sequencing, and TMAO levels were measured in plasma using a Vantera® Clinical Analyzer. 102 ESLD patients, of which 23 with PVT, and 246 healthy controls were included. No significant difference in gut microbiome diversity was found between patients with PVT and without PVT (P=0.18). Both ESLD groups had significantly lower alpha-diversity compared with controls. Bacteroides fragilis and three Clostridiales species were increased in patients with PVT compared to without PVT. TMAO levels between the three groups were not significantly different. We observed profound differences in gut microbiota between ESLD patients and controls, but minimal differences between ESLD patients with or without PVT. In our cohort, a gut-derived pro-inflammatory state was not associated with presence of PVT in ESLD patients.

Prognostic Value of Serum TMAO Measurement in Patients with STEMI: A Systematic Literature Review.

Gut microbiota-derived metabolite Trimethylamine-N-oxide (TMAO) is increasingly recognized as a potential novel prognostic biomarker for cardiovascular disease. Our research work aimed to investigate the potential utility of TMAO measurement in patients with STelevation Myocardial Infarction (STEMI). We performed a systematic literature search in PubMed from inception to the 1st of February 2024 to identify all studies examining the association between plasma TMAO levels and disease complexity or clinical outcomes in STEMI patients. A total of eight prospective cohort studies were included, encompassing a total of 2,378 STEMI patients. Three of the studies provided only in-hospital evidence (i.e., increased odds for more severe coronary artery disease, plaque rupture, and plaque healing in patients with increased TMAO levels). Four studies examined the long-term prognostic value of TMAO after 10-12 months of follow-up post-STEMI (i.e., increased risk of adverse cardiovascular events in patients with increased TMAO levels), while one study provided data for both in-hospital and mid-term prognosis, indicating that 4-months after STEMI patients with greater TMAO elevation had larger infarct size. Higher TMAO levels were associated with a greater prevalence of high-risk coronary plaque characteristics and worse in-hospital and follow-up outcomes in STEMI patients. Further study is needed on whether modulating the diet-dependent TMAO levels could improve clinical outcomes in these patients. [(OSF): https://doi.org/10.17605/OSF.IO/WNG8V].

Impacts of intestinal microbiota metabolite trimethylamine N-oxide on cardiovascular disease: a bibliometric analysis.

Trimethylamine N-oxide (TMAO), a metabolite dependent on intestinal microbiota, is closely related to the emergence, progression, and prognosis of cardiovascular disease (CVD), and has received increasing attention in recent years. The current research hotspots and future development trends in TMAO and CVD field are found through bibliometrics analysis, which provides reference for further study. The bibliometrics tools VOSviewer and CiteSpace were used to analyze the publications from the Web of Science Core Collection (WOSCC) database. The articles published from 2004 to 2024 about the relationship between TMAO and CVD were retrieved. Bibliometric analysis includes annual publications, countries/regions, institutions, authors and co-cited authors, journals and cited-journals, references and keywords. After searching and screening, 1,466 publications were included for subsequent bibliometric analysis. Since 2014, the number of publications exposing the relationship between TMAO and CVD has increased rapidly, as has the frequency of citations. China, USA and Italy are the countries that publish the most relevant research. Cleveland Clinic is the leading institution in this field. Stanley L Hazen, Zeneng Wang and W H Wilson Tang are the most prolific authors in this field, and the latter two have the closest academic cooperation. American Journal of Clinical Nutrition and Journal of the American Heart Association are influential journals that publish research in this field. "Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk" is the most frequently cited article. Keyword analysis shows that gut microbiota, metabolism, phosphatidylcholine and atherosclerosis (AS) are the hotspots in this field. This study summarizes the research situation of TMAO and CVD in the past 20 years, focusing on the effect of TMAO on pathogenesis of AS, predictive value of TMAO on CVD risk, and dietary and drug intervention for TMAO. Probiotics and natural products may be the research focus of preventing and treating CVD by intervening TMAO in the future.

Gut Microbiota at the Crossroad of Hepatic Oxidative Stress and MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition marked by excessive lipid accumulation in hepatic tissue. This disorder can lead to a range of pathological outcomes, including metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Despite extensive research, the molecular mechanisms driving MASLD initiation and progression remain incompletely understood. Oxidative stress and lipid peroxidation are pivotal in the "multiple parallel hit model", contributing to hepatic cell death and tissue damage. Gut microbiota plays a substantial role in modulating hepatic oxidative stress through multiple pathways: impairing the intestinal barrier, which results in bacterial translocation and chronic hepatic inflammation; modifying bile acid structure, which impacts signaling cascades involved in lipidic metabolism; influencing hepatocytes' ferroptosis, a form of programmed cell death; regulating trimethylamine N-oxide (TMAO) metabolism; and activating platelet function, both recently identified as pathogenetic factors in MASH progression. Moreover, various exogenous factors impact gut microbiota and its involvement in MASLD-related oxidative stress, such as air pollution, physical activity, cigarette smoke, alcohol, and dietary patterns. This manuscript aims to provide a state-of-the-art overview focused on the intricate interplay between gut microbiota, lipid peroxidation, and MASLD pathogenesis, offering insights into potential strategies to prevent disease progression and its associated complications.