Trimethylamine N-oxide Concentrations Research Articles

Mo(IV) Ion-Modulated BSA-Protected Gold Nanocluster Probe for Fluorescence Turn-On Detection of Trimethylamine N-Oxide (TMAO).

Trimethylamine N-oxide (TMAO), a molecule produced by the microbiota, has been associated with human health and illness. Its early discovery in body fluids may affect our understanding of the pathophysiology and treatment of many illnesses. Therefore, our knowledge of the pathophysiology and diagnostics of disorders associated with TMAO might be enhanced by the creation of dependable and fast methods for TMAO detection. Therefore, we developed a fluorescent probe for detecting TMAO utilizing an on-off-on strategy. Bovine serum albumin (BSA)@AuNCs luminescence is effectively quenched by Mo4+ because BSA@AuNCs and Mo4+ have a strong binding relationship. Mo4+ ions can substantially decrease the emission intensity of gold nanoclusters by establishing a BSA@AuNCs-Mo system. Then, the luminescence of BSA@AuNCs was restored due to the interaction between Mo4+ and TMAO. A significant linear relationship was seen between the emission intensity and TMAO concentration within the 0-201 μM range, with a detection limit of 1.532 μM. Additionally, the method can measure TMAO in blood and urine samples.

Intra-hospital variation of gut microbiota product, trimethylamine N-oxide (TMAO), predicts future major adverse cardiovascular events after myocardial infarction

ObjectiveTrimethylamine N-oxide (TMAO) has been associated with atherosclerosis and poor outcome. We evaluated the prognostic impact of intra-hospital TMAO variation on patient outcome. Methods and ResultsBlood samples from 149 patients with acute myocardial infarction (AMI) were taken on admission and discharge. Plasma TMAO was determined by HPLC-MS. The endpoint was a composite three-point MACE (major adverse cardiovascular events), including all-cause mortality, re-infarction, or heart failure (HF) development. Median TMAO concentration on admission was significantly higher than on discharge (respectively, 7.81 [3.47–19.98] vs 3.45 [2.3–4.78] μM, p < 0.001). After estimating the 3.45 μM TMAO cut-off with the analysis of the continuous hazard ratio, we divided our cohort into two groups. The first group included 75 (50.3%) patients whose TMAO levels remained below or decreased under cut-off (low-low/high-low; LL/HL), while the second group included 74 (49.7%) patients whose TMAO levels remained high or increased above the cut-off during hospitalisation (high-high/low-high; HH/LH). During the median 30-month follow-up, 21.5% of patients experienced the composite endpoint. At Kaplan-Meier analysis, a trend of increasing MACE risk was observed in patients in the HH/LH group (p = 0.05). At multivariable Cox analysis, patients from the HH/LH group had more than two times higher risk of MACE during the follow-up than the LL/HL group (HR = 2.15 [95% CI, 1.03–4.5], p = 0.04). Other independent predictors of MACE were older age and worse left ventricular systolic function. ConclusionIn patients with AMI, permanently high or increasing TMAO levels during hospitalisation are associated with a higher risk of MACE during long-term follow-up.

Plasma Concentrations of Trimethylamine-N-Oxide, Choline, and Betaine in Patients With Moderate to Advanced Chronic Kidney Disease and Their Relation to Cardiovascular and Renal Outcomes

Trimethylamine N-oxide (TMAO) is a gut bacteria mediated liver metabolite of dietary betaine, choline, and carnitine which is excreted by glomerular filtration. We studied whether TMAO is associated with cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Among 478 patients with CKD stage G2 (n = 104), G3a (n = 163), G3b (n = 123), and G4 (n = 88), we studied the association between fasting plasma concentrations of TMAO, choline or betaine at baseline and kidney function, prevalent CVD and future renal outcomes during a mean follow-up of 5.1 years. Decreased glomerular filtration rate was associated with higher plasma concentrations of TMAO, choline and betaine. Baseline concentrations of TMAO were higher in participants with preexisting CVD compared to those without CVD (8.4 [10.1] vs. 7.8 [8.0] μmol/L; p = 0.047), but the difference was not significant after adjusting for confounders. During the follow up, 147 participants experienced CVD or died and 144 reached the predefined renal endpoint. In the adjusted regression analyses, TMAO or choline concentrations in the upper three quartiles (versus the lowest quartile) were not associated with any of the study clinical endpoints. In contrast, the adjusted hazard ratio of plasma betaine in the highest quartile versus the lowest quartile was 2.14 (1.32, 3.47) for the CVD endpoint and 1.64 (1.00, 2.67) for the renal endpoint. Elevated plasma TMAO concentrations were explained by impaired kidney function. Elevated plasma concentrations of betaine, but not that of TMAO or choline predicted adverse outcomes. TMAO might not be an appropriate target to reduce CVD or renal outcomes in patients with preexisting CKD.

Trimethylamine-N-Oxide and Related Metabolites: Assessing Cardiovascular Risk in the Dallas Heart Study

ObjectiveTo evaluate the association between trimethylamine N-oxide (TMAO) and related metabolites with adverse cardiovascular events in a multiethnic urban primary prevention population. MethodsWe performed a case-control study of 361 participants of the Dallas Heart Study, including 88 participants with an incident atherosclerotic cardiovascular disease (ASCVD) event and 273 controls matched for age, sex, and body mass index without an ASCVD event during 12 years of follow-up (January 1, 2000, through December 31, 2015). Plasma levels of TMAO, choline, carnitine, betaine, and butyrobetaine were measured by mass spectrometry. The differential odds for incident ASCVD by metabolite levels between cases and controls were compared by a conditional logistic regression model adjusted for cardiovascular risk factors. ResultsParticipants with incident ASCVD had higher levels of TMAO and related metabolites compared with those without ASCVD (P<.05 for all). Those with plasma TMAO concentrations in quartile 4 had a more than 2-fold higher odds of ASCVD compared with those in quartile 1 (odds ratio, 2.77 [95% CI, 1.05 to 7.7; P=.04] for hard ASCVD and 2.41 [95% CI, 1.049 to 5.709; P=.04]). Similar trends were seen with the related metabolites choline, betaine, carnitine, and butyrobetaine. ConclusionOur results suggest that TMAO and related metabolites are independently associated with ASCVD events. Although further studies are needed, measurement of TMAO and related metabolites may have a role in ASCVD risk stratification for primary prevention.

Trimethylamine-N-oxide, a New Risk Factor for Non-alcoholic Fatty Liver Disease Changes the Expression of miRNA-34a, and miRNA-122 in the Fatty Liver Cell Model.

Non-alcoholic fatty liver disease is a multifactorial disorder with complicated pathophysiology ranging from simple steatosis to steatohepatitis and liver fibrosis. Trimethylamine-N-oxide (TMAO) production is believed to be correlated with choline deficiency. This study investigated the expression of miRNA-34a, miRNA-122, and miRNA-192 in the fatty liver cell model treated with different concentrations of TMAO. A fatty liver cell model was developed by exposing HepG2 cells to a mixture of palmitate and oleate in a ratio of 1:2 at a final concentration of 1200μM for 24h. The confirmed fatty liver cells were treated with 37.5, 75, 150, and 300μM of TMAO for 24h. RT-qPCR was used to quantify the expression of microRNAs in a cellular model. The cellular expression of all microRNAs was significantly higher in treated fatty liver cells compared to normal HepG2 cells (P < 0.05). Only 75 and 150µM of TMAO significantly increased the expression of miRNA-34a and miRNA-122 compared to both fatty and normal control cells (P < 0.05). Our results provided an experimental documentation for the potential effect of TMAO to change the expression of miR-34a and miR-22 as a mechanism for contributing to the pathogenesis of non-alcoholic fatty liver disease.

Abstract P397: Choline Metabolites Are Associated With Non-Alcoholic Fatty Liver Disease: A Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Non-alcoholic fatty liver disease (NAFLD), a common cause of chronic liver disease, has become increasingly prevalent. Choline deficiency has long been a model for the study of accelerated NAFLD, in preclinical and small-scale human studies. More recently, NAFLD has been associated with choline metabolites betaine (inversely) and trimethylamine N-oxide (TMAO) (positively). There has been a paucity of research on circulating choline metabolites and NAFLD in diverse and population-based cohort studies. Methods: We used data from 2,413 CARDIA participants who did not self-report liver disease or heavy alcohol intake at Y15, had stored plasma available from Y15, and chest computed tomography (CT) measures from Y25. NAFLD was defined as a mean CT-derived liver attenuation score &lt;51 Hounsfield units; severe NAFLD was &lt;40 Hounsfield units. Liquid chromatography mass spectrometry was used to quantify choline, betaine, and TMAO concentrations from stored plasma samples. Plasma metabolite concentrations were standardized for analysis. Plasma TMAO was natural log transformed for normality. Multivariable-adjusted logistic regression models quantified associations between plasma choline metabolites and NAFLD. Results (Table): In fully adjusted models, plasma betaine was inversely associated with NAFLD, and plasma TMAO was positively associated with NAFLD. Plasma choline was not associated with NAFLD in fully adjusted models. Conclusions: Our findings support an inverse association between plasma betaine and NAFLD in a diverse, population-based US cohort, and a positive association between plasma TMAO and NAFLD. Circulating betaine reflects dietary intake of betaine, as well as conversion from choline. TMAO reflects an alternative fate of choline, through metabolism by the gut microbiota. These results contribute to a growing literature on choline metabolism and cardiometabolic risk.

Pharmacokinetics of soy-derived lysophosphatidylcholine compared with that of glycerophosphocholine: a randomized controlled trial.

Lysophosphatidylcholine (LPC) is present in various foods and contains a choline moiety such as in glycerophosphocholine (GPC). However, the potential of LPC as a choline source remains unclear. This study investigated the single-dose pharmacokinetics of 480 mg soy-derived LPC in 12 healthy men compared with that of either soy oil with the same lipid amount (placebo) or GPC with the same choline amount. Both LPC and GPC supplementation increased plasma choline, serum phospholipid, and serum triglyceride concentrations, but neither of them significantly elevated plasma trimethylamine N-oxide concentration. In addition, although the intake of LPC slightly increased plasma LPC16:0, LPC18:2, and total LPC concentrations, their concentrations remained within physiological ranges. No adverse events were attributed to the LPC supplementation. To the best of our knowledge, this study is the first to compare LPC and GPC pharmacokinetics in humans and show that LPC can be a source of choline.

STUDY OF DIETARY REMODELING OF THE INTESTINAL MICROBIOTA BY GRAPE POLYPHENOLS AT THE LEVEL OF TRIMETHYLAMINE N-OXIDE (TMAO) IN PATIENTS WITH ACUTE CORONARY SYNDROME WITH ELEVATION OF THE SEGMENT ST

The main cause of mortality and disability in the adult population of our planet is cardiovascular diseases caused by atherosclerosis. The relevance of research into new methods of treating atherosclerosis is only increasing. In addition to dyslipedemia, infections and inflammation, new predictors of atherogenesis are being sought, and one of them is the level of trimethylamine N-oxide (TMAO). Many large studies have shown that circulating TMAO levels correlate with the development of atherosclerosis. In turn, the formation of TMAO depends on the state of the intestinal microbiome. That is, the stages of development of atherosclerosis can be influenced by changes in the intestinal microbiome. Purpose: Based on domestic and foreign scientific publications, to determine the effect of dietary remodeling of the gut microbiota by grape polyphenols on trimethylamine N-oxide (TMAO) levels in patients with STsegment elevation acute coronary syndrome. Results and conclusions: It was revealed that in patients with STEMI, the use of the prebiotic Kainar with grape polyphenols changes the concentration of TMAO in the blood. It was confirmed that there were statistically significant differences in TMAO values in the control group and the group taking Kaynar after 3 months and after 12 months.

Trimethylamine N-oxide, choline and its metabolites are associated with the risk of non-alcoholic fatty liver disease.

It is inconclusive whether trimethylamine N-oxide (TMAO) and choline and related metabolites, namely trimethylamine (TMA), l-carnitine, betaine and dimethylglycine (DMG), are associated with non-alcoholic fatty liver disease (NAFLD). Our objective was to investigate these potential associations. Additionally, we sought to determine the mediating role of TMAO. In this 1:1 age- and sex-matched case-control study, a total of 150 pairs comprising NAFLD cases and healthy controls were identified. According to the fully adjusted model, after the highest tertile was compared with the lowest tertile, the plasma TMAO concentration (OR = 2·02 (95 % CI 1·04, 3·92); P trend = 0·003), l-carnitine concentration (OR = 1·79 (1·01, 3·17); P trend = 0·020) and DMG concentration (OR = 1·81 (1·00, 3·28); P trend = 0·014) were significantly positively associated with NAFLD incidence. However, a significantly negative association was found for plasma betaine (OR = 0. 50 (0·28, 0·88); P trend = 0·001). The restricted cubic splines model consistently indicated positive dose-response relationships between exposure to TMAO, l-carnitine, and DMG and NAFLD risk, with a negative association being observed for betaine. The corresponding AUC increased significantly from 0·685 (0·626, 0·745) in the traditional risk factor model to 0·769 (0·716, 0·822) when TMAO and its precursors were included (l-carnitine, betaine and choline) (P = 0·032). Mediation analyses revealed that 14·7 and 18·6 % of the excess NAFLD risk associated with l-carnitine and DMG, respectively, was mediated by TMAO (the P values for the mediating effects were 0·021 and 0·036, respectively). These results suggest that a higher concentration of TMAO is associated with increased NAFLD risk among Chinese adults and provide evidence of the possible mediating role of TMAO.

Potential Association of the Oral Microbiome with Trimethylamine N-Oxide Quantification in Mexican Patients with Myocardial Infarction.

Many attempts have been proposed to evaluate the linkage between the oral-gut-liver axis and the mechanisms related to the diseases' establishment. One of them is the oral microbiota translocation into the bloodstream, liver, and gut, promoting a host dysbiosis and triggering the presence of some metabolites such as trimethylamine N-oxide (TMAO), known as a risk marker for cardiovascular disease, and especially the myocardial infarction (MI). In the present pilot study, the involvement of oral dysbiosis related to the presence of TMAO has been considered an independent component of the standard risk factors (SRs) in the development of MI, which has not been previously described in human cohorts. A positive and significant correlation of TMAO levels with Porphyromonas was identified; likewise, the increase of the genus Peptidiphaga in patients without SRs was observed. We determined that the presence of SRs does not influence the TMAO concentration in these patients. This report is the first study where the relationship between oral dysbiosis and TMAO is specified in the Mexican population. Our findings provide information on the possible contribution of the oral pathogens associated with gut dysbiosis in the development of MI, although further analysis should be performed.

Red meat intake, faecal microbiome, serum trimethylamine N-oxide and hepatic steatosis among Chinese adults.

Emerging evidence suggests a detrimental impact of high red meat intake on hepatic steatosis. We investigated the potential interplay between red meat intake and gut microbiome on circulating levels of trimethylamine N-oxide (TMAO) and hepatic steatosis risk. This cross-sectional study was conducted in a representative sample of 754 community-dwelling adults in Huoshan, China. Diet was collected using 4 quarterly 3 consecutive 24-h dietary (12-day) recalls. We profiled faecal microbiome using 16S ribosomal RNA sequencing and quantified serum TMAO and its precursors using LC-tandem MS (n = 333). We detected hepatic steatosis by FibroScan. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression. TMAO levels but not its precursors were positively associated with the likelihood of hepatic steatosis (aOR per 1-SD increment 1.86, 95% CI 1.04-3.32). We identified 14 bacterial genera whose abundance was associated with TMAO concentration (pFDR < .05) belonging to the phyla Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria families. Per 10 g/day increase in red meat intake was positively associated with TMAO levels among participants who had higher red meat intake (>70 g/day) and higher TMAO-predicting microbial scores (TMS, β = .045, p = .034), but not among others (pinteraction = .030). TMS significantly modified the positive association between red meat and steatosis (pinteraction = .032), with a stronger association being observed among participants with higher TMS (aOR 1.30, 95% CI 1.07-1.57). The bacterial genera that predicted TMAO levels may jointly modify the association between red meat intake and TMAO levels and the subsequent risk of hepatic steatosis.

Effect of trimethylamine-N-oxide on the phase separation of aqueous polyethylene glycol-600-Dextran-75 two-phase systems.

The emergence of phase separation in both intracellular biomolecular condensates (membrane-less organelles) and in vitro aqueous two-phase systems (ATPS) relies on the formation of immiscible water-based phases/domains. The solvent properties and arrangement of hydrogen bonds within these domains have been shown to differ and can be modulated with the addition of various inorganic salts and osmolytes. The naturally occuring osmolyte, trimethylamine-N-oxide (TMAO), is well established as a biological condensate stabilizer whose presence results in enhanced phase separation of intracellular membrane-less compartments. Here, we show the unique effect of TMAO on the mechanism of phase separation in model PEG-600-Dextran-75 ATPS using dynamic and static light scattering in conjunction with ATR-FTIR and solvatochromic analysis. We observe that the presence of TMAO may enhance or destabilize phase separation depending on the concentration of phase forming components. Additionally, the behavior and density of mesoscopic polymer agglomerates, which arise prior to macroscopic phase separation, are altered by the presence and concentration of TMAO.

The Association Between the Gut Microbiome and COVID-19 Severity: The Potential Role of TMAO Produced by the Gut Microbiome

Context: The COVID-19 pandemic has had profound impacts on public health, resulting in nearly 1 million deaths. Emerging evidence suggests an association between certain metabolites produced by gut microbiota and potential alterations in the severity of infection. Trimethylamine N-oxide (TMAO) is a waste metabolite generated by gut microbes from dietary choline and betaine. Evidence Acquisition: Several investigations have indicated an association between serum TMAO concentrations and the development of inflammation and thrombosis. Trimethylamine N-oxide, produced by the gut microbiome in a state of dysbiosis, upregulates various molecular mechanisms, such as the nuclear factor kappa (NF-kB) molecular pathway, and promotes the expression of scavenger receptors (SRs) on the surfaces of macrophages, leading to foam cell formation and inflammation. High levels of TMAO have been shown to induce the expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β) while reducing the expression of anti-inflammatory cytokines such as interleukin-10 (IL-10). Additionally, gut-derived TMAO enhances platelet aggregation and adhesion to collagen, increasing the risk of thrombosis. Conclusions: Understanding the association between gut microbiome compositions such as gut TMAO and their effects on SARS-CoV-19 infection progression helps to control disease severity. In this review, we presented a hypothesis that the gut TMAO has the potential to increase COVID-19 disease severity.

Comparison of the low-calorie DASH diet and a low-calorie diet on serum TMAO concentrations and gut microbiota composition of adults with overweight/obesity: a randomized control trial

This study compares two diets, Dietary Approaches to Stop Hypertension (DASH) and a Low-Calorie Diet on Trimethylamine N-oxide (TMAO) levels and gut microbiota. 120 obese adults were randomly allocated to these three groups: a low-calorie DASH diet, a Low-Calorie diet, or a control group for 12 weeks. Outcomes included plasma TMAO, lipopolysaccharides (LPS), and gut microbiota profiles. After the intervention, the low-calorie DASH diet group demonstrated a greater decrease in TMAO levels (-20 ± 8.1 vs. −10.63 ± 4.6 μM) and a significant decrease in LPS concentration (-19.76 ± 4.2 vs. −5.68 ± 2.3) compared to the low-calorie diet group. Furthermore, the low-calorie DASH diet showed a higher decrease in the Firmicutes and Bactericides (F/B) ratio, which influenced TMAO levels, compared to the Low-Calorie diet (p = 0.028). The current study found the low-calorie DASH diet improves TMAO and LPS in comparison to a Low-Calorie diet.

Higher serum trimethylamine N-oxide (TMAO) levels are associated with increased visceral fat in hemodialysis patients.

Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has emerged as a new potentially important cause of increased atherosclerosis and cardiovascular risk in chronic kidney disease (CKD) patients. However, the possible causes whereby TMAO potentiates atherosclerosis development remain poorly defined. The strong association between gut microbiota and obesity suggested that the TMAO pathway may be linked to the pathogenesis of obesity. A total of 184 hemodialysis (HD) patients and 38 healthy controls were enrolled in the study from March 2019 to May 2019. We evaluated visceral fat area (VFA) by anthropometric measurement and measured serum TMAO concentrations using liquid chromatography/differential ion mobility spectrometry tandem mass spectrometry. We also examined the relationship between TMAO levels and visceral fat accumulation. TMAO level was markedly higher in HD patients than in control subjects (5.80 (3.96, 9.46) vs. 0.18 (0.11, 0.32) µg/mL, p<0.01), and its level in diabetic HD patients was significantly higher than in nondiabetic patients (6.93 (4.67, 11.40) vs. 5.25 (3.78, 8.02) µg/mL, p<0.01). A significant positive correlation was found between serum TMAO level and VFA in these patients (r=0.282, p=0.005). Multiple regression analysis showed that Ln(TMAO) was independently associated with Ln(VFA) in HD patients (p=0.008). Our results showed that there was a significant positive correlation between serum TMAO levels and visceral fat in HD patients, which suggested that TMAO may predict cardiovascular risk through increased visceral fat.

Study of the influence of GLP-1 receptor agonists on the metabolic activity of the intestinal microbiota in patients with type 2 DM

The aim: to investigate the peculiarities of the metabolic activity of the intestinal microbiota in patients with type 2 diabetes under the influence of glucagon-like peptide-1 receptor agonist therapy. Materials and methods: 21 patients with type 2 diabetes mellitus were included in the study, the average age was 57.2±8.53 years (M±SD), the HbA1c level was 8.29±0.88 % (M±SD). Patients were prescribed raGLP-1 at the maximum tolerated dose for 6 months. Before and after the course of treatment, indicators of body composition were determined by the bioelectrical impedance method (TANITA BC-545N analyzer, Japan), characteristics of carbohydrate metabolism and the lipid spectrum of blood serum, as well as the concentration of GLP-1, trimethylamine-N-oxide (TMAO) by the immunoenzymatic method, of short-chain fatty acids (SCFA) by the method of chromatographic research. Results. After 6 months of therapy with liraglutide against the background of a statistically significant decrease in fasting blood glucose and HbA1c levels (p&lt;0.05), a decrease in body mass index and waist circumference (p&lt;0.05), a decrease in the content of visceral (p&lt;0.05 ) and total fat (p&lt;0.05) in patients with type 2 diabetes, there was a decrease in the concentration of TMAO in blood serum (p&lt;0.05) and an increase in the concentration of SCFA: acetic, propionic (p&lt;0.05) in the coprofiltrate and a tendency to increase in the level of butyric acids. Data analysis also established an increase in the concentration of endogenous GLP-1 in the blood (p&lt;0.05). Conclusions. The detected changes in microbial metabolites may indicate a positive effect of raGLP-1 on the composition of the intestinal microbiota and its metabolic activity in patients with T2DM, which in turn contributes to the improvement of endogenous secretion of incretins

The effects of incretin mimetics on the level of the microbial metabolite trimethylamine-N-oxide, a marker of cardiovascular risk in type 2 diabetic patients

Background. The purpose was to investigate the effect of therapy with glucagon-like peptide-1 receptor agonists (GLP-1ra) on the serum concentration of trimethylamine-N-­oxide (TMAO), an intestinal microbiome metabolite, in patients with type 2 diabetes mellitus (T2DM) in relation to clinical and laboratory indicators and parameters of body composition. Materials and methods. Thirty-three T2DM patients (17 women and 16 men) were examined aged 31 to 72 years who had unsatisfactory control of carbohydrate metabolism (HbA1c &gt; 7.4 %) against the background of previous glucose-lowering therapy (metformin, sulfonylurea derivatives, insulin, gliflozin) and were administered GLP-1ra. Before the start of treatment and after 6 months of therapy, parameters of anthropometry, body composition were measured (using the bioelectrical impedance analysis with the Tanita analyzer); blood glucose and glycated hemoglobin, TMAO concentration, blood lipids were assessed. Results. Patients diagnosed with Т2DM had HbA1c &gt; 7.4 %; 91 % had general obesity (body mass index 34.7 ± 6.6 kg/m2), 100 % had abdominal obesity (waist circumference 118.00 ± 11.24 cm, Med ± SD). In 72 % of cases, there was a history of cardiovascular complications (myocardial infarction, stroke, coronary and peripheral atherosclerosis, arterial stenosis). Under the influence of a 6-month administration of GLP1ra, there was a decrease in the degree of total and abdominal obesity, a significant drop in the percentage of fat and the level of visceral fat, which was accompanied by an increase in hydration, a reduction in triglyceridemia and the concentration of very-low-density lipoprotein cholesterol (VLDL-C). A significant decrease in the level of TMAO microbial metabolite in the blood serum was recorded, which may reflect the antiatherogenic effect of GLP1ra, associated with the control of cholesterol and bile acid metabolism, the stimulation of VLDL-C receptors, and the effect on the secretion of insulin, glucagon, ghrelin, leptin, incretins. Conclusions. A study on the clinical effects of the incretin mimetic (GLP-1ra) in patients with T2DM confirmed its positive impact on glucose metabolism and blood lipids. At the same time, during GLP-1ra therapy, an improvement of some compositional and lipid indicators (visceral fat, triglycerides, VLDL-C) was recorded with a simultaneous decrease in the concentration of TMAO toxic metabolite.

Acute changes in the metabolome following resistance exercise combined with intake of different protein sources (cricket, pea, whey).

Separately, both exercise and protein ingestion have been shown to alter the blood and urine metabolome. This study goes a step further and examines changes in the metabolome derived from blood, urine and muscle tissue extracts in response to resistance exercise combined with ingestion of three different protein sources. In an acute parallel study, 52 young males performed one-legged resistance exercise (leg extension, 4 × 10 repetitions at 10 repetition maximum) followed by ingestion of either cricket (insect), pea or whey protein (0.25g protein/kg fat free mass). Blood and muscle tissue were collected at baseline and three hours after protein ingestion. Urine was collected at baseline and four hours after protein ingestion. Mixed-effects analyses were applied to examine the effect of the time (baseline vs. post), protein (cricket, pea, whey), and time x protein interaction. Nuclear magnetic resonance (NMR)-based metabolomics resulted in the annotation and quantification of 25 metabolites in blood, 35 in urine and 21 in muscle tissue. Changes in the muscle metabolome after combined exercise and protein intake indicated effects related to the protein source ingested. Muscle concentrations of leucine, methionine, glutamate and myo-inositol were higher after intake of whey protein compared to both cricket and pea protein. The blood metabolome revealed changes in a more ketogenic direction three hours after exercise reflecting that the trial was conducted after overnight fasting. Urinary concentration of trimethylamine N-oxide was significantly higher after ingestion of cricket than pea and whey protein. The blood, urine and muscle metabolome showed different and supplementary responses to exercise and ingestion of the different protein sources, and in synergy the summarized results provided a more complete picture of the metabolic state of the body.

The relationship between trimethylamine-N-oxide and the risk of acute ischemic stroke: A dose‒response meta-analysis.

Although trimethylamine-N-oxide (TMAO) shows a notable correlation with cardiovascular disease, its association with acute ischemic stroke (AIS) remains uncertain and necessitates further investigation. A meta-analysis was conducted to assess the relationship between trimethylamine-N-oxide and acute ischemic stroke. We conducted a comprehensive search in PubMed, Embase, Cochrane, CNKI, VIP, Wanfang, and CBM, spanning from their inception to 23 September 2023. The search was consistently updated and supplemented by bibliographies of retrieved articles and previous reviews. A total of 20 eligible studies, including 17 case‒controls and 3 cohort studies, were selected, involving 9141 participants (5283 case group, 3858 control group). For the dose‒response analysis, three case-control studies were eligible. We extracted and pooled TMAO mean and standard deviation from observational studies for control and ischemic stroke groups. The effect sizes were combined using the random-effects model. Where possible, dose‒response analysis was performed. Overall, the pooled standardized mean difference (SMD) demonstrated significantly higher concentrations of serum/plasma TMAO in AIS compared to the control group (SMD = 1.27; 95% CI: 0.9, 1.61, P<0.001). Additionally, the dose‒response meta-analysis revealed a 12.1% relative increase in the risk of acute ischemic stroke per 1 μmol/L rise in TMAO concentration (RR = 1.12; 95% CI 1.07-1.17; P<0.05; I2 = 1.6%, P = 0.4484). These findings indicate a potential increased risk of AIS associated with elevated TMAO levels.

Targeted Plasma Metabolomics Reveals Association of Acute Myocardial Infarction Risk with the Dynamic Balance between Trimethylamine-N-oxide, Betaine, and Choline.

The relationship between trimethylamine-N-oxide (TMAO), betaine, and choline with acute myocardial infarction (AMI) end point remains unclear. We analyzed plasma TMAO, betaine, and choline concentrations in AMI cases and non-AMI community-dwelling controls by LC-MS/MS to understand how the balance between these metabolites helps to reduce AMI risk. Results showed that the odds ratio (OR) for the highest versus lowest quartiles of betaine was 0.30 (95% CI, 0.10-0.82) after adjustment for AMI risk factors, and the unadjusted OR for quartile 3 versus quartile 1 of TMAO was 2.47 (95% CI, 1.02-6.17) (p < 0.05). The study populations with "high betaine + low TMAO" had a significant protective effect concerning AMI with a multivariable-adjusted OR of 0.20 (95% CI, 0.07-0.55) (p < 0.01). Multivariate linear regression showed that the chronological age was correlated with TMAO concentrations among AMI patients (95% CI, 0.05-3.24, p < 0.01) but not among the controls. This implies a further potential interplay between age and metabolite combination─AMI risk association.