[Effect analysis of trimethylamine N-oxide and its precursors on susceptibility to pancreatic diseases].

OBJECTIVE: To investigate the causal relationship between trimethylamine N-oxide (TMAO) and its precursors (betaine, carnitine, and choline) and pancreatic diseases based on the Mendelian randomization (MR) method. METHODS: Genome-wide association study data of TMAO, betaine, carnitine, choline, acute pancreatitis (AP), chronic pancreatitis (CP), pancreatic cancer (PC), and circulating immune cell characteristics (white blood cell, lymphocyte, monocyte, neutrophil, eosinophil and basophil) were collected. According to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines, the available genetic variants [single nucleotide polymorphism (SNP)] were strictly screened. The causal relationship between exposure (TMAO and its precursors) and outcomes (pancreatic diseases and circulating immune cell characteristics) was evaluated using inverse variance weighting (IVW), MR-Egger regression and weighted median. The reliability of the results was evaluated by sensitivity analysis based on MR-Egger regression, MR-PRESSO, Cochrane's Q test and leave-one-out method. RESULTS: A total of 36 SNP associated with TMAO and its precursors were included. Five of these were associated with TMAO, 13 with betaine, 12 with carnitine, and 6 with choline. (1) MR analysis showed that TMAO may increase the risk of AP [odds ratio (OR) = 1.100, 95% confidence interval (95%CI) was 1.008-1.200, P = 0.032], and choline may reduce the risk of alcoholic acute pancreatitis (AAP; OR = 0.743, 95%CI was 0.585-0.944, P = 0.015). The analysis results of MR-Egger regression and weighted median were consistent with the IVW results. There is no evidence to support a causal relationship between TMAO and its precursors and the risk of CP and PC. Sensitivity analysis indicated that SNP analyzed by MR showed no heterogeneity and low pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. (2) There was a positive causal relationship between plasma TMAO level and circulating monocyte count (OR = 1.017, 95%CI was 1.000*-1.034, P = 0.048, * represented that the data was obtained by correcting to 3 decimal places from 1.000 1). The causal effect obtained by MR-Egger regression and weighted median analysis was consistent with the results of IVW. Sensitivity analysis illustrated SNP analyzed by MR showed no heterogeneity and pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. CONCLUSIONS: TMAO and choline may change the risk of AP, and TMAO may contribute to the increase of circulating monocyte count in AP.

Microbiome-derived metabolite effects on intestinal barrier integrity and immune cell response to infection.

The gut microbiota exerts a significant influence on human health and disease. While compositional changes in the gut microbiota in specific diseases can easily be determined, we lack a detailed mechanistic understanding of how these changes exert effects at the cellular level. However, the putative local and systemic effects on human physiology that are attributed to the gut microbiota are clearly being mediated through molecular communication. Here, we determined the effects of gut microbiome-derived metabolites l-tryptophan, butyrate, trimethylamine (TMA), 3-methyl-4-(trimethylammonio)butanoate (3,4-TMAB), 4-(trimethylammonio)pentanoate (4-TMAP), ursodeoxycholic acid (UDCA), glycocholic acid (GCA) and benzoate on the first line of defence in the gut. Using in vitro models of intestinal barrier integrity and studying the interaction of macrophages with pathogenic and non-pathogenic bacteria, we could ascertain the influence of these metabolites at the cellular level at physiologically relevant concentrations. Nearly all metabolites exerted positive effects on barrier function, but butyrate prevented a reduction in transepithelial resistance in the presence of the pathogen Escherichia coli, despite inducing increased apoptosis and exerting increased cytotoxicity. Induction of IL-8 was unaffected by all metabolites, but GCA stimulated increased intra-macrophage growth of E. coli and tumour necrosis-alpha (TNF-α) release. Butyrate, 3,4-TMAB and benzoate all increased TNF-α release independent of bacterial replication. These findings reiterate the complexity of understanding microbiome effects on host physiology and underline that microbiome metabolites are crucial mediators of barrier function and the innate response to infection. Understanding these metabolites at the cellular level will allow us to move towards a better mechanistic understanding of microbiome influence over host physiology, a crucial step in advancing microbiome research.

Highly diverse-Low abundance methanogenic communities in hypersaline microbial mats of Guerrero Negro B.C.S., assessed through microcosm experiments.

Methanogenic communities of hypersaline microbial mats of Guerrero Negro, Baja California Sur, Mexico, have been recognized to be dominated by methylotrophic methanogens. However, recent studies of environmental samples have evidenced the presence of hydrogenotrophic and methyl-reducing methanogenic members, although at low relative abundances. Physical and geochemical conditions that stimulate the development of these groups in hypersaline environments, remains elusive. Thus, in this study the taxonomic diversity of methanogenic archaea of two sites of Exportadora de Sal S.A was assessed by mcrA gene high throughput sequencing from microcosm experiments with different substrates (both competitive and non-competitive). Results confirmed the dominance of the order Methanosarcinales in all treatments, but an increase in the abundance of Methanomassiliiccocales was also observed, mainly in the treatment without substrate addition. Moreover, incubations supplemented with hydrogen and carbon dioxide, as well as the mixture of hydrogen, carbon dioxide and trimethylamine, managed to stimulate the richness and abundance of other than Methanosarcinales methanogenic archaea. Several OTUs that were not assigned to known methanogens resulted phylogenetically distributed into at least nine orders. Environmental samples revealed a wide diversity of methanogenic archaea of low relative abundance that had not been previously reported for this environment, suggesting that the importance and diversity of methanogens in hypersaline ecosystems may have been overlooked. This work also provided insights into how different taxonomic groups responded to the evaluated incubation conditions.

Metabolic mediators: microbial-derived metabolites as key regulators of anti-tumor immunity, immunotherapy, and chemotherapy.

The human microbiome has recently emerged as a focal point in cancer research, specifically in anti-tumor immunity, immunotherapy, and chemotherapy. This review explores microbial-derived metabolites, emphasizing their crucial roles in shaping fundamental aspects of cancer treatment. Metabolites such as short-chain fatty acids (SCFAs), Trimethylamine N-Oxide (TMAO), and Tryptophan Metabolites take the spotlight, underscoring their diverse origins and functions and their profound impact on the host immune system. The focus is on SCFAs' remarkable ability to modulate immune responses, reduce inflammation, and enhance anti-tumor immunity within the intricate tumor microenvironment (TME). The review critically evaluates TMAO, intricately tied to dietary choices and gut microbiota composition, assessing its implications for cancer susceptibility, progression, and immunosuppression. Additionally, the involvement of tryptophan and other amino acid metabolites in shaping immune responses is discussed, highlighting their influence on immune checkpoints, immunosuppression, and immunotherapy effectiveness. The examination extends to their dynamic interaction with chemotherapy, emphasizing the potential of microbial-derived metabolites to alter treatment protocols and optimize outcomes for cancer patients. A comprehensive understanding of their role in cancer therapy is attained by exploring their impacts on drug metabolism, therapeutic responses, and resistance development. In conclusion, this review underscores the pivotal contributions of microbial-derived metabolites in regulating anti-tumor immunity, immunotherapy responses, and chemotherapy outcomes. By illuminating the intricate interactions between these metabolites and cancer therapy, the article enhances our understanding of cancer biology, paving the way for the development of more effective treatment options in the ongoing battle against cancer.

Effect of an acute session of intermittent exercise on trimethylamine N-oxide (TMAO) production following choline ingestion.

INTRODUCTION: Trimethylamine N-oxide (TMAO) is a gut bacteria-dependent metabolite associated with poor cardiovascular health. Exercise is a known cardioprotective activity but the impact of an acute bout of exercise on TMAO production is unknown. OBJECTIVES/METHODS: This study assessed choline-derived production of TMAO following a single bout of intermittent exercise in a young, healthy cohort. RESULTS: Choline supplemented after either exercise or a time-matched resting period demonstrated a similar increase in circulating TMAO across an 8-hour period. CONCLUSION: This suggests that a single bout of intermittent exercise does not alter gut microbial metabolic behaviour and thus does not provide additional cardioprotective benefits related to blood levels of TMAO.

Investigation of electrocatalysis for tiered-tower micro-electro-mechanical-system-based biosensors: application in the early detection of the thrombosis factor trimethylamine N-oxide.

Trimethylamine N-oxide (TMAO) has been recognized as a biomarker for the early detection of thrombosis. However, testing for TMAO typically requires expensive laboratory equipment and skilled technicians, making it unsuitable for home care pre-screening. To enable its widespread use in home applications, it is crucial to develop a scalable and sensitive device capable of catalyzing TMAO metabolism with a specific enzyme that is tailored for point-of-care use. This study presents an investigation of a MEMS-based two-tiered-tower biosensor array with a detection limit of 0.1 µM for TMAO, aiming to diagnose chronic metabolic diseases using urine or serum samples. Based on the augmented Cole-Cole model, the proposed parameters R_catalyzed, C_catalyzed, and Rp_catalyzed can predict the catalytic impedance of enzymatic activities such as the redox effects of analytes and characterize the small-signal current caused by catalysis. The proposed MEMS biosensor, integrated with a readout circuitry, demonstrates a high sensitivity of 41 ADC counts per µM TMAO (or 4.5 mV µM-1 TMAO), a response time of 1 second, a repetition rate of 98.9%, and a drift over time of 0.5 mV. The sensor effectively distinguishes TMAO based on minute capacitance changes induced by the TorA enzyme, resulting in a discernible distinction of 10.6%. These measurements were successfully compared to conventional cyclic voltammetry (CV) results, showing a variance of only 0.024%. The proposed biosensor is well-suited for pre-screening thrombosis factors for the early detection and prevention of thrombosis in point-of-care applications. The device is cost-effective, lightweight, and demonstrates excellent performance, with a conversion rate of 88% of TMAO and a selectivity rate of 97% for the by-product TMA, allowing for the prediction of cardiovascular risks.

Gut Microbiota and Metabolic Alterations Associated with Heart Failure and Coronary Artery Disease.

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

Metabolite, Biochemical, and Dietary Intake Alterations Associated with Lifestyle Interventions in Obese and Overweight Malaysian Women.

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

Native Mass Spectrometry of Membrane Protein-Lipid Interactions in Different Detergent Environments.

Native mass spectrometry (MS) reveals the role of specific lipids in modulating membrane protein structure and function. Membrane proteins solubilized in detergents are often introduced into the mass spectrometer. However, detergents commonly used for structural studies, such as dodecylmaltoside, tend to generate highly charged ions, leading to protein unfolding, thereby diminishing their utility in characterizing protein-lipid interactions. Thus, there is a critical need to develop approaches to investigate protein-lipid interactions in different detergents. Here, we demonstrate how charge-reducing molecules, such as spermine and trimethylamine-N-oxide, enable the opportunity to characterize lipid binding to the bacterial water channel (AqpZ) and ammonia channel (AmtB) in complex with regulatory protein GlnK in different detergent environments. We find that protein-lipid interactions not only are protein-dependent but also can be influenced by the detergent and type of charge-reducing molecule. AqpZ-lipid interactions are enhanced in LDAO (n-dodecyl-N,N-dimethylamine-N-oxide), whereas the interaction of AmtB-GlnK with lipids is comparable among different detergents. A fluorescent lipid binding assay also shows detergent dependence for AqpZ-lipid interactions, consistent with results from native MS. Taken together, native MS will play a pivotal role in establishing optimal experimental parameters that will be invaluable for various applications, such as drug discovery as well as biochemical and structural investigations.

The interaction between dietary nitrates/nitrites intake and gut microbial metabolites on metabolic syndrome: a cross-sectional study.

Background: Metabolic syndrome (MetS) prevalence has increased globally.The evidence shows thatdiet and gut microbial metabolites includingtrimethylamine N-oxide (TMAO) and kynurenine (KYN) play an important role in developing MetS. However, there is a lack of evidence on associations between between diet and these metabolites. This study aimed to investigate the interaction between dietary nitrate/nitrite and gut microbial metabolites (TMAO, KYN) on MetS and its components. Methods: This cross-sectional study included 250 adults aged 20-50 years. Dietary intake was assessed using food frequency questionnaires (FFQ), and serum TMAO and KYN levels were measured. MetS was defined usingthe National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria. Result: The ATPIII index revealed an 11% prevalence of metabolic syndrome among the study participants. After adjusting for confounders, significant positive interactions were found: High animal-source nitrate intake and high TMAO levels with elevated triglycerides (TG) (p interaction = 0.07) and abdominal obesity (p interaction = 0.08). High animal-source nitrate intake and high KYN levels with increased TG (p interaction = 0.01) and decreased high-density lipoprotein cholesterol (HDL) (p interaction = 0.01).Individuals with high animal-source nitrite intake and high TMAO levels showed increased risk of hypertriglyceridemia (OR: 1.57, 95%CI: 0.35-2.87, p = 0.05), hypertension (OR: 1.53, 95%CI: 0.33-2.58, p = 0.06), and lower HDL (OR: 1.96, 95%CI: 0.42-2.03, p = 0.04). Similarly, high animal-source nitrite intake with high KYN levels showed lower HDL (OR: 2.44, 95%CI: 1.92-3.89, p = 0.07) and increased risk of hypertension (OR: 2.17,95%CI: 1.69-3.40, p = 0.05). Conversely, Negative interactions were found between high plant-source nitrate/nitrite intake with high KYN and TMAO levels on MetS and some components. Conclusion: There is an interaction between dietary nitrate/nitrite source (animal vs. plant) and gut microbial metabolites (TMAO and KYN) on the risk of of MetS and its components. These findings highlight the importance of considering diet, gut microbiome metabolites, and their interactions in MetS risk assessment.

The Effect of Dietary Types on Gut Microbiota Composition and Development of Non-Communicable Diseases: A Narrative Review.

INTRODUCTION: The importance of diet in shaping the gut microbiota is well established and may help improve an individual's overall health. Many other factors, such as genetics, age, exercise, antibiotic therapy, or tobacco use, also play a role in influencing gut microbiota. AIM: This narrative review summarizes how three distinct dietary types (plant-based, Mediterranean, and Western) affect the composition of gut microbiota and the development of non-communicable diseases (NCDs). METHODS: A comprehensive literature search was conducted using the PubMed, Web of Science, and Scopus databases, focusing on the keywords "dietary pattern", "gut microbiota" and "dysbiosis". RESULTS: Both plant-based and Mediterranean diets have been shown to promote the production of beneficial bacterial metabolites, such as short-chain fatty acids (SCFAs), while simultaneously lowering concentrations of trimethylamine-N-oxide (TMAO), a molecule associated with negative health outcomes. Additionally, they have a positive impact on microbial diversity and therefore are generally considered healthy dietary types. On the other hand, the Western diet is a typical example of an unhealthy nutritional approach leading to an overgrowth of pathogenic bacteria, where TMAO levels rise and SCFA production drops due to gut dysbiosis. CONCLUSION: The current scientific literature consistently highlights the superiority of plant-based and Mediterranean dietary types over the Western diet in promoting gut health and preventing NCDs. Understanding the influence of diet on gut microbiota modulation may pave the way for novel therapeutic strategies.

Gut microbiota metabolite trimethylamine N-oxide promoted NAFLD progression by exacerbating intestinal barrier disruption and intrahepatic cellular imbalance.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, with the gut microbiota and its metabolites are important regulators of its progression. Trimethylamine N-oxide (TMAO), a metabolite of the gut microbiota, has been closely associated with various metabolic diseases, but its relationship with NAFLD remains to be elucidated. In this study, we found that fecal TMAO levels correlated with NAFLD severity. Moreover, TMAO promoted lipid deposition in HepG2 fatty liver cells and exacerbated hepatic steatosis in NAFLD rats. In the colon, TMAO undermined the structure and function of the intestinal barrier at various levels, further activated the TLR4/MyD88/NF-κB pathway, and inhibited the WNT/ß-catenin pathway. In the liver, TMAO induced endothelial dysfunction with capillarization of liver sinusoidal endothelial cells, while modulating macrophage polarization. In conclusion, our study suggests that gut microbiota metabolite TMAO promotes NAFLD progression by impairing the gut and liver and that targeting TMAO could be an alternative therapeutic strategy for NAFLD.

Trimethylamine N-oxide promotes PERK-mediated endothelial-mesenchymal transition and apoptosis thereby aggravates atherosclerosis.

The endothelial-mesenchymal transition (EndMT) is involved in the development of atherosclerosis (AS) and is a key process in vascular endothelial injury. Oxidative stress, inflammation, and apoptosis are common causes of EndMT, and EndMT progression can further accelerate the development of AS. The metabolite trimethylamine N-oxide (TMAO) is produced by the gut microbiome and is implicated in the development of several diseases, including diabetes and chronic kidney disease. However, the impact of TMAO on transforming growth factor ß1(TGF-ß1)-induced EndMT remains unclear. We hypothesize that TMAO exacerbates plaque formation and cardiac function impairment by promoting EndMT. Herein, we showed that high serum TMAO levels caused plaque formation, cardiac function damage and haemodynamic changes in ApoE-/- mice. In vitro, TMAO upregulated mesenchymal markers and downregulated endothelial markers in HAECs. Furthermore, TMAO increased the migratory capacity of EndMT cells. Mechanistically, we found that PERK downregulation could alleviate TMAO-induced oxidative stress, EndMT, plaque formation and cardiac function damage. Further study showed that activated transcription factor 3 (ATF3), the downstream molecule of protein kinase RNA-like endoplasmic reticulum kinase (PERK), could bind with TGF-ß1/2 and affect EndMT. Overall, TMAO promotes EndMT, possibly through the PERK-eIF2α-ATF4-CHOP or the PERk-eIF2α-ATF3-TGF-ß signalling pathways.

Effects of Trimethylamine N-Oxide in Improving Exercise Performance in Mice: A 1H-NMR-Based Metabolomic Analysis Approach.

To improve exercise performance, the supplement of nutrients has become a common practice before prolonged exercise. Trimethylamine N-oxide (TMAO) has been shown to ameliorate oxidative stress damage, which may be beneficial in improving exercise capacity. Here, we assessed the effects of TMAO on mice with exhaustive swimming, analyzed the metabolic changes, and identified significantly altered metabolic pathways of skeletal muscle using a nuclear magnetic resonance-based (NMR-based) metabolomics approach to uncover the effects of TMAO improving exercise performance of mice. We found that TMAO pre-administration markedly prolonged the exhaustive time in mice. Further investigation showed that TMAO pre-administration increased levels of 3-hydroxybutyrate, isocitrate, anserine, TMA, taurine, glycine, and glutathione and disturbed the three metabolic pathways related to oxidative stress and protein synthesis in skeletal muscle. Our results provide a metabolic mechanistic understanding of the effects of TMAO supplements on the exercise performance of skeletal muscle in mice. This work may be beneficial in exploring the potential of TMAO to be applied in nutritional supplementation to improve exercise performance. This work will lay a scientific foundation and be beneficial to exploring the potential of TMAO to apply in nutritional supplementation.

Treatment with Gac Fruit Extract and Probiotics Reduces Serum Trimethylamine N-Oxide in Chronic Kidney Disease Rats.

Chronic kidney disease (CKD) affects more than 850 million people worldwide, contributing to morbidity and mortality, particularly through cardiovascular disease (CVD). The altered composition in CKD patients leads to increased production and absorption of uremic toxins such as trimethylamine (TMA) and its oxidized form, trimethylamine N-oxide (TMAO), which are associated with cardiovascular risks. This study investigated the potential of supplementary interventions with high-carotenoid-content gac fruit extract and probiotics to mitigate serum TMAO by modulating the gut microbiota. We conducted an animal study involving 48 male Wistar rats, divided into six groups: the control, CKD control, and four treatment groups receiving gac fruit extract, carotenoid extract, or combinations with Ligilactobacillus salivarius and Lactobacillus crispatus and Lactobacillus casei as a standard probiotic. CKD was induced in rats using cisplatin and they were supplemented with choline to enhance TMA production. The measures included serum creatinine, TMAO levels, gut microbiota composition, and the expression of fecal TMA lyase and intestinal zonula occluden-1 (ZO-1). CKD rats showed increased TMA production and elevated serum levels of TMAO. Treatment with gac fruit extract and selective probiotics significantly altered the composition of the gut microbiota by decreasing Actinobacteriota abundance and increasing the abundance of Bacteroides. This combination effectively promoted ZO-1 expression, reduced fecal TMA lyase, and subsequently lowered serum TMAO levels, demonstrating the therapeutic potential of these interventions. Our results highlight the benefits of gac fruit extract combined with probiotics for the effective reduction in serum TMAO levels in rats with CKD, supporting the further exploration of dietary and microbial interventions to improve outcomes in patients with CKD.

Targeted metabolomics reveals the contribution of degradation and oxidation of lipids and proteins mediated by pH to the formation of characteristic volatiles in preserved egg yolk during pickling.

Targeted metabolomics and flavouromics combined with relative odor activity value were performed to explore the effect of degradation and oxidation of matrix mediated by pH on the formation of characteristic volatiles in preserved egg yolk (PEY) during pickling. It was found that the oxidation of proteins and lipids in PEY induced by pH sequentially occurred in early and later periods, and degradation both mainly occurred in early stage. Moreover, 1-octen-3-one, heptanal, trimethylamine, etc., compounds and 5-HETrE, proline, etc., components were confirmed as up-regulated characteristic volatiles and differential metabolites in PEY during pickling. The formation of octanal-M/D and benzeneacetaldehyde-M was attributed to ß-oxidation of hydroxyeicosapentaenoic acid and L-isoleucine catalyzed by strong alkali at early period based on correlation network between them, respectively. Meanwhile, the generation of 1-octen-3-one-M/D mainly depended on L-serine and could be promoted by phosphatidylcholines oxidation. At later stage, the formation of heptanal-M/D was primarily attributed to phosphatidylethanolamines oxidation induced by alkali, and the enrichment of heptanal-M/D and nonanal were both enhanced by oxidized lipids. Lastly, trimethylamine was derived from L-lysine under alkaline conditions and promoted by protein oxidation during the whole process. This manuscript provided insight into the differential contribution of oxidation and degradation from matrix regulated by exogenous factors on the formation pathway for characteristic volatiles in foods.

Gut microbiota metabolites and risk of major adverse cardiovascular events and death: A systematic review and meta-analysis.

BACKGROUND: Gut microbial metabolites such as trimethylamine N-oxide (TMAO) and its precursors, namely betaine, L-carnitine, and choline, have been implicated as risk factors for cardiovascular events and mortality development. Therefore, we aim to perform a systematic review and meta-analysis to assess the validity of these associations. METHODS: MEDLINE and Scopus were queried from their inception to August 2023 to identify studies that quantified estimates of the associations of TMAO with the development of major adverse cardiovascular events (MACE) or death. A random-effects meta-analysis was conducted to pool unadjusted or multivariable-adjusted hazard ratios (HR) and their 95% confidence intervals. The primary endpoint was the risk of MACE and all-cause death. RESULTS: 30 prospective observational studies (n = 48 968) were included in the analysis. Elevated TMAO levels were associated with a significantly greater risk of MACE and all-cause death compared to low TMAO levels (HR: 1.41, 95% CI 1.2-1.54, P < .00001, I2 = 43%) and (HR: 1.55, 95% CI 1.37-1.75, P < .00001, I2 = 46%), respectively. Furthermore, high levels of either L-carnitine or choline were found to significantly increase the risk of MACE. However, no significant difference was seen in MACE in either high or low levels of betaine. CONCLUSION: Elevated concentrations of TMAO were associated with increased risks of MACE and all-cause mortality. High levels of L-carnitine/choline were also significantly associated with an increased risk of MACE. However, no significant difference was found between high or low levels of betaine for the outcome of MACE.

Rapid and Facile Synthesis of Homoporous Colorimetric Films Using Leaf Vein-Mediated Emulsion Evaporation Method for Visual Monitoring of Food Freshness.

A new method for rapid and facile fabrication of homoporous films with high volatile amine sensitivity was developed. First, red cabbage anthocyanin was encapsulated in ethyl cellulose to form water-in-organic (W/O) emulsion. Afterward, the W/O emulsion was rapidly dried using the supporting matrix Magnolia Grandiflora Linn leaf vein at 60% relative humidity and 50 °C to form a colorimetric film with regular hexagonal pores with an average side length of about 23 µm. The films exhibited good sensitivity to ammonia (NH3), dimethylamine, and trimethylamine, with limit of detection of 0.26, 0.24, and 0.38 µM, respectively, and high stability when stored in high humid environments. An obvious color change of the films from pink to green was clearly observed during the freshness monitoring of pork, chicken, salmon, and shrimp. Thus, this work offered a novel and reliable method for the development of porous films for food freshness monitoring.

GPR40/GPR120 Agonist GW9508 Improves Metabolic Syndrome-Exacerbated Periodontitis in Mice.

G protein-coupled receptor (GPR)40 and GPR120 are receptors for medium- and long-chain free fatty acids. It has been well documented that GPR40 and GPR120 activation improves metabolic syndrome (MetS) and exerts anti-inflammatory effects. Since chronic periodontitis is a common oral inflammatory disease initiated by periodontal pathogens and exacerbated by MetS, we determined if GPR40 and GPR120 activation with agonists improves MetS-associated periodontitis in animal models in this study. We induced MetS and periodontitis by high-fat diet feeding and periodontal injection of lipopolysaccharide, respectively, and treated mice with GW9508, a synthetic GPR40 and GPR120 dual agonist. We determined alveolar bone loss, osteoclast formation, and periodontal inflammation using micro-computed tomography, osteoclast staining, and histology. To understand the underlying mechanisms, we further performed studies to determine the effects of GW9508 on osteoclastogenesis and proinflammatory gene expression in vitro. Results showed that GW9508 improved metabolic parameters, including glucose, lipids, and insulin resistance. Results also showed that GW9508 improves periodontitis by reducing alveolar bone loss, osteoclastogenesis, and periodontal inflammation. Finally, in vitro studies showed that GW9508 inhibited osteoclast formation and proinflammatory gene secretion from macrophages. In conclusion, this study demonstrated for the first time that GPR40/GPR120 agonist GW9508 reduced alveolar bone loss and alleviated periodontal inflammation in mice with MetS-exacerbated periodontitis, suggesting that activating GPR40/GPR120 with agonist GW9508 is a potential anti-inflammatory approach for the treatment of MetS-associated periodontitis.

Trimethylamine-N-oxide and 5-year mortality: the role of gut microbiota-generated metabolite from the CORE-Thailand cohort.

The gut microbiota metabolite trimethylamine-N-oxide (TMAO)-derived from dietary phosphatidylcholine-is mechanistically linked to cardiovascular disease (CVD) and increased cardiovascular risk. This study examined the relationship between fasting plasma TMAO levels and 5-year all-cause mortality in a cohort of patients at high risk of cardiovascular events (CORE-Thailand Registry). Of the 134 patients, 123 (92%) had established cardiovascular disease, and 11 (8%) had multiple risk factors. Fasting plasma TMAO levels were measured using nuclear magnetic resonance spectroscopy. Within this prospective cohort study, the median TMAO was 3.81 µM [interquartile range (IQR) 2.89-5.50 µM], with a mean age of 65 ± 11 years; 61% were men, and 39.6% had type II diabetes. Among 134 patients, 65 (49%) were identified as the high-TMAO group (≥ 3.8 µM), and 69 (51%) were identified as the low-TMAO group (< 3.8 µM). After a median follow-up of 58.8 months, the high-TMAO group was associated with a 2.88-fold increased mortality risk. Following adjustment for traditional risk factors, high-sensitivity cardiac troponin-T, estimated glomerular filtration rate, angiotensin-converting enzyme (ACEI), or angiotensin-receptor blocker (ARB) use, the high-TMAO group remained predictive of 5-year all-cause mortality risk (the high-TMAO vs. the low-TMAO group, adjusted hazard ratio 2.73, 95% CI 1.13-6.54; P = 0.025). Among Thai patients at high risk of cardiovascular events, increased plasma TMAO levels portended greater long-term mortality risk.