Search Results (420)

The oral–gut microbiota axis is a relatively new field of research. Although most studies have focused separately on the oral and gut microbiota, emerging evidence has highlighted that the two microbiota are interconnected and may influence each other through various mechanisms shaping systemic health. The aim of this review is therefore to provide an overview of the interactions between oral and gut microbiota, and the influence of diet and related metabolites on this axis. Pathogenic oral bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, can migrate to the gut through the enteral route, particularly in individuals with weakened gastrointestinal defenses or conditions like gastroesophageal reflux disease, contributing to disorders like inflammatory bowel disease and colorectal cancer. Bile acids, altered by gut microbes, also play a significant role in modulating these microbiota interactions and inflammatory responses. Oral bacteria can also spread via the bloodstream, promoting systemic inflammation and worsening some conditions like cardiovascular disease. Translocation of microorganisms can also take place from the gut to the oral cavity through fecal–oral transmission, especially within poor sanitary conditions. Some metabolites including short-chain fatty acids, trimethylamine N-oxide, indole and its derivatives, bile acids, and lipopolysaccharides produced by both oral and gut microbes seem to play central roles in mediating oral–gut interactions. The complex interplay between oral and gut microbiota underscores their crucial role in maintaining systemic health and highlights the potential consequences of dysbiosis at both the oral and gastrointestinal level. Some dietary patterns and nutritional compounds including probiotics and prebiotics seem to exert beneficial effects both on oral and gut microbiota eubiosis. A better understanding of these microbial interactions could therefore pave the way for the prevention and management of systemic conditions, improving overall health outcomes. Full article

Gut microbiota-derived trimethylamine N-oxide (TMAO) has been implicated in both intestinal and renal diseases; however, its specific role in modulating gut–kidney interactions remains unclear. This study aimed to investigate the effects of TMAO on gut–kidney crosstalk using a mouse model of diarrhea. Mice were divided into four groups: normal, model, TMAO, and TMAO + model. The normal group received sterile water, while the other groups were administered adenine + Folium sennae, TMAO, or a combination of TMAO and adenine + Folium sennae. Samples were collected to assess morphological changes in the colon and kidney, evaluate the colonic mucosal barrier and renal function, and measure NLRP3 inflammasome activity and inflammatory cytokine levels in colonic and renal tissues. TMAO levels and the gut microbiota composition were analyzed using 16S rRNA sequencing. The model group exhibited altered stool morphology, which was further aggravated by TMAO intervention. Both the model and TMAO + model groups exhibited significant damage to intestinal and renal tissues, along with compromised intestinal mucosal barriers and impaired renal function compared to controls. Inflammatory markers were elevated in these groups, with the TMAO + model group showing the most pronounced increases. Correlation analysis indicated significant relationships among TMAO levels, inflammasome activation, and inflammatory cytokines. The genera Mucispirillum and Anaerotruncus negatively correlated with TMAO, whereas Parabacteroides and Parasutterella genera positively correlated with TMAO. In conclusion, TMAO plays a critical role in modulating gut–kidney crosstalk by promoting inflammation, disrupting mucosal and renal integrity, and altering the gut microbial ecosystem. Full article

Cardiac surgery, particularly procedures involving cardiopulmonary bypass (CPB), is associated with a high risk of postoperative complications, including systemic inflammatory response syndrome (SIRS), postoperative atrial fibrillation (POAF), and infection. Growing evidence suggests that the gut–heart axis, through mechanisms involving intestinal barrier integrity and gut microbiota homeostasis, may influence these outcomes. This review summarizes the relationship between gut microbiota composition and the inflammatory response in patients undergoing cardiac surgery and the extent to which these alterations impact clinical outcomes. The reviewed studies consistently show that cardiac surgery induces notable alterations in microbial diversity and composition during the perioperative period. These changes, indicative of dysbiosis, are characterized by a reduction in health-associated bacteria such as Blautia, Faecalibacterium, and Bifidobacterium and an increase in opportunistic pathogens. Inflammatory biomarkers were frequently elevated postoperatively, even in patients without evident complications. Key microbial metabolites and biomarkers, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and bile acids (BAs), were implicated in modulating inflammation and clinical outcomes. Additionally, vitamin D deficiency emerged as a contributing factor, correlating with increased systemic inflammation and a higher incidence of POAF. The findings suggest that gut microbiota composition prior to surgery may influence the severity of the postoperative inflammatory response and that perioperative modulation of the gut microbiota could represent a novel approach to improving surgical outcomes. However, the relationship between dysbiosis and acute illness in surgical patients is confounded by factors such as antibiotic use and other perioperative interventions. Large-scale, standardized clinical studies are needed to better define these interactions and guide future therapeutic strategies in cardiac surgery. Full article

Trimethylamine N-oxide (TMAO) is known to increase in human cardiovascular, metabolic, and renal diseases. In human medicine, TMAO has recently been utilized as a diagnostic and prognostic biomarker for renal dysfunction, and research is ongoing regarding its potential as a therapeutic target. This study aimed to evaluate the diagnostic and prognostic potential of TMAO as a supportive biomarker in dogs with chronic kidney disease (CKD). To assess its diagnostic utility, TMAO concentrations were compared between a CKD group (n = 32) and a healthy control group (n = 32). In addition, patients with CKD were subdivided into stages 2 (n = 12), 3 (n = 11), and 4 (n = 9) and compared individually with the healthy controls. For prognostic evaluation, the CKD group was monitored over six months, and the TMAO levels were compared between survivors (n = 18) and non-survivors (n = 14). The TMAO concentrations showed a highly significant difference between patients with CKD and healthy controls (p < 0.0001). Patients with each different CKD stage exhibited statistically significant differences compared with the healthy controls (p < 0.05). Furthermore, the median TMAO levels tended to increase with advancing CKD stage; however, the differences among stages were not statistically significant. In addition, within the CKD group, TMAO concentrations were significantly higher in non-survivors than in survivors at the six-month follow-up (p = 0.0142). This pilot study highlights the potential of TMAO as a supportive renal biomarker for diagnostic and prognostic evaluation in canine CKD. Full article

Autism spectrum disorder (ASD) is increasingly associated with microbial and metabolic disturbances, including the altered production of gut-derived uremic toxins. We investigated urinary concentrations of five representative uremic toxins—indoxyl sulfate (IS), p-cresyl sulfate (PCS), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)—in 161 children with ASD and 71 healthy controls. Toxins were measured using LC-MS/MS and were normalized to creatinine. Subgroup analyses were performed by sex, age group (2–5.9 vs. 6–17 years), and autism severity based on the Childhood Autism Rating Scale (CARS). In addition to individual concentrations, we calculated the total toxin burden, proportional contributions, and functional ratios (IS/PCS, PCS/TMAO, and IS/ADMA). While individual toxin levels did not differ significantly between groups, stratified analyses revealed that PCS was higher in girls and in severe cases of ASD, whereas IS and TMAO were reduced in younger and more severely affected children. The functional ratios shifted consistently with severity—IS/PCS declined from 1.69 in controls to 0.99 in severe cases of ASD, while PCS/TMAO increased from 12.2 to 20.5. These patterns suggest a phenolic-dominant microbial signature and an altered host–microbial metabolic balance in ASD. Functional toxin profiling may offer a more sensitive approach to characterizing metabolic disturbances in ASD than concentration analysis alone. Full article

A comprehensive bibliometric analysis of literature is imperative to elucidate current research landscapes and hotspots in the interplay between gut microbiota and hypertension, identify knowledge gaps, and establish theoretical foundations for the future. We used publications retrieved from the Web of Science Core Collection (WoSCC) and SCOPUS databases (January 2001–December 2024) to analyze the annual publication trends with GraphPad Prism 9.5.1, to evaluate co-authorship, keywords clusters, and co-citation patterns with VOSviewer 1.6.20, and conducted keyword burst detection and keyword co-occurrence utilizing CiteSpace v6.4.1. We have retrieved 2485 relevant publications published over the past 24 years. A 481-fold increase in global annual publications in this field was observed. China was identified as the most productive country, while the United States demonstrated the highest research impact. For the contributor, Yang Tao (University of Toledo, USA) and the University of Florida (USA) have emerged as the most influential contributors. Among journals, the highest number of articles was published in Nutrients (n = 135), which also achieved the highest citation count (n = 5397). The emergence of novel research hotspots was indicated by high-frequency keywords, mainly “hypertensive disorders of pregnancy”, “mendelian randomization”, “gut-heart axis”, and “hepatitis B virus”. “Trimethylamine N-oxide (TMAO)” and “receptor” may represent promising new research frontiers in the gut microbiota–hypertension nexus. The current research trends are shifting from exploring the factors influencing gut microbiota and hypertension to understanding the underlying mechanisms of these factors and the potential therapeutic applications of microbial modulation for hypertension management. Full article

Background/Objectives: Trimethylamine N-oxide (TMAO) is implicated in the development of atherosclerosis and cardiovascular diseases. Preventive strategies must recognize the excessive consumption of products rich in choline, carnitine, and betaine, which are substrates essential for TMAO synthesis. The aim of this study was to develop and validate a dietary questionnaire to assess the consumption of these compounds and investigate the correlation with serum TMAO levels in a Central European population. Methods: A dietary questionnaire was designed based on a literature review identifying foods high in TMAO precursors. The tool was validated in a prospective study with 94 participants. The theoretical relevance and reliability of the tool were assessed using factor analysis and statistical indices. Reproducibility was evaluated in a subgroup of 10 participants who completed the questionnaire a second time 24 h later. The results of the questionnaire helped us to determine factors contributing to serum TMAO levels. Results: The final questionnaire consisted of 15 questions, providing acceptable data quality (KMO = 0.654). Three main dietary factors were detected: (1) the consumption of fish products and legumes (SS loadings = 1.72; 10.78% variance), (2) the consumption of cereal products and root vegetables (SS loadings = 1.61; 10.05% variance), and (3) the consumption of meat (SS loadings = 1.47; 9.22% variance). Conclusions: The validated questionnaire is a useful tool for assessing the intake of TMAO-promoting foods in post-myocardial infarction patients from Central Europe. It may support dietary risk assessment and nutritional counseling in clinical practice, particularly for secondary cardiovascular prevention. Full article

Background/Objectives: Trimethylamine (TMA), produced by gut microbiota, and its derivative trimethylamine N-oxide (TMAO) are both associated with cardiometabolic diseases. While the effects of high-fat diets (HFDs) and high-disaccharide diets (HDDs) on gut microbiota in the context of obesity have been well studied, their impact on TMA/TMAO production, particularly alongside physiological caloric intake, remains obscure. This study investigates how standard HFDs and HDDs alongside physiological caloric intake influence gut microbiota composition and TMA/TMAO production in rats. Methods: Sprague Dawley rats were fed one of three diets a standard diet, an HFD, or an HDD for 12 weeks, with chow availability adjusted by age to maintain physiological caloric intake. Gut bacterial diversity was analyzed using 16S rRNA gene sequencing, and metabolites were quantified via High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) in urine and plasma. Results: The HFD group had significantly higher urinary levels of TMA and TMAO compared to the control and HDD groups. Gut bacterial diversity in the HFD group was markedly reduced, displaying the lowest species richness and phylogenetic diversity among all the groups. Notably, Pasteurellaceae (within the order Pasteurellales) and S24-7 (within the order Bacteroidales) were positively correlated with TMAO levels. The demonstrated HDD group increased microbial diversity compared to both the control and HFD groups. Conclusions: A high-fat diet during controlled and physiological caloric intake increases TMA/TMAO production and reduces gut microbial diversity. This underscores the role of diet composition, beyond caloric excess, in shaping gut microbiota and the related cardiometabolic biomarkers. Full article

This review examines human digestive physiology and metabolic adaptations in the context of evolutionary dietary patterns, particularly those emphasizing carnivorous and scavenging behaviors. By integrating metabolomic data with archaeological, anatomical, and microbiological evidence, the study explores how early hominins adapted to intermittent but energy-dense animal-based diets. The analysis highlights the development of hepatic insulin resistance, enhanced fat and protein metabolism, and shifts in gut microbiota diversity as physiological signatures of meat consumption. Comparative evaluations of digestive enzyme profiles, intestinal morphology, and salivary composition underscore humans’ omnivorous flexibility and partial carnivorous specialization. Additionally, biomarkers such as ketone bodies, branched-chain amino acids, and trimethylamine-N-oxide are identified as metabolic indicators of habitual meat intake. These adaptations, though once evolutionarily advantageous, are discussed in relation to current metabolic disorders in modern nutritional contexts. Overall, this review presents a metabolomic framework for understanding the evolutionary trajectory of human digestion and its implications for health and dietary recommendations. Full article

Declining kidney function contributes to the accumulation of uraemic toxins produced by gut microbiota, leading to the uraemic syndrome. This study aimed to identify associations between uraemic toxins, diet quality, symptoms and the gut microbiota in individuals initiating peritoneal dialysis. A cross-sectional analysis of baseline data from participants in a longitudinal study was conducted. Symptom scores using the Integrated Palliative Care Outcomes Scale-Renal were recorded. Plasma p-Cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide were measured using liquid chromatography-mass spectrometry. Gut microbiota was determined using 16S rRNA sequencing. Multivariate linear models examined associations across the cohort. Data from 43 participants (mean age 61 ± 13 years; 70% male; median eGFR 7 mL/min/1.73 m²) were analysed. Diabetes was the primary cause of kidney disease (51.2%). Patients were classified into ‘high’ (n = 18) and ‘low’ (n = 26) uraemic toxin groups using K-means clustering. The ‘high’ group had a lower eGFR (p < 0.05) but no differences in diet quality or symptom scores. Significant differences in alpha and beta diversity were observed between the groups (p = 0.01). The ‘high’ group had increased Catenibacterium, Prevotella, Clostridia, and decreased Ruminococcus gnavus abundances. Multivariate models identified 32 genera associated with uraemic toxins, including positive associations of Oscillospiraceae UCG-002 and UCG-005 with p-cresyl sulfate, and negative associations with Actinomyces and Enterococcus. Patients with kidney failure initiating peritoneal dialysis have distinct uraemic toxin profiles, associated with differences in microbial diversity. This phenotype was also associated with differences in residual kidney function but not with diet or symptom severity. Longitudinal studies are required to determine causality and guide therapeutic interventions. Full article

Type 2 diabetes (T2D) is a major global health issue, influenced by sedentary behavior and obesity. Emerging evidence implicates the gut microbiota in T2D pathophysiology through effects on glucose metabolism, inflammation, and insulin sensitivity. This systematic review included eleven studies, six observational and five interventional, examining the relationship between physical activity, exercise, and gut microbiota in individuals with or at risk of T2D. Observational studies associated low physical activity and high sedentary time with reduced α-diversity and increased abundance of potentially harmful bacteria. Interventional studies showed that structured exercise, including moderate-intensity and sprint interval training, increased beneficial bacteria such as Faecalibacterium, Veillonella, Lachnospira, and Bifidobacterium, linked to anti-inflammatory effects and improved metabolic profiles. However, overall microbial diversity often remained unchanged unless combined with dietary modifications. Exercise also reduced levels of trimethylamine N-oxide, a metabolite linked to cardiovascular risk. Despite increases in butyrate-producing taxa, most studies did not report significant short-term changes in short-chain fatty acid levels, highlighting the complex interaction between microbiota and host metabolism. These findings support physical activity and exercise as modifiable factors that can influence gut microbiota composition, potentially contributing to improved metabolic regulation and better management of T2D. Full article

Background: Chronic non-communicable diseases (NCDs) are a major global health challenge, with unhealthy diets contributing significantly to their burden. Metabolomics data offer new possibilities for identifying nutritional biomarkers, as demonstrated in short-term intervention studies. This study investigated associations between habitual dietary intake and urinary metabolites, a not well-studied area. Methods: Data were available from 496 participants of the population-based MEIA study. Linear and median regression models examined associations between habitual dietary intake and metabolites, adjusted for possible confounders. K-means clustering identified urinary metabolite clusters, and multinomial regression models were applied to analyze associations between food intake and metabolite clusters. Results: Using linear regression models, previously reported associations could be replicated, including citrus intake with proline betaine, protein intake with urea, and fiber intake with hippurate. Novel findings include positive associations of poultry intake with taurine, indoxyl sulfate, 1-methylnicotinamide, and trimethylamine-N-oxide. Milk substitutes were positively associated with urinary uracil, pseudouridine, 4-hydroxyhippurate, and 3-hydroxyhippurate, and inversely associated with quinic acid. Dietary fiber intake showed a positive association with 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and a negative association with indoxyl sulfate. We identified sucrose and taurine as key metabolites differentiating metabolite clusters. Multinomial regression analysis confirmed significantly different dietary associations across clusters, particularly for fruits, processed meat, poultry, and alcoholic beverages. Conclusions: This study highlights established and novel food–metabolite associations, demonstrating the potential of urinary metabolomics for use as nutritional biomarkers in individuals from the general population. Full article

Trimethylamine N-oxide (TMAO), a gut microbiome metabolite linked to cardiovascular health, can be influenced by dietary factors like choline intake and diet quality. This study compared the effects of mixed tree nuts (MTNs) and pretzels, as part of a 12-week hypocaloric weight loss diet, on TMAO levels and identified dietary predictors. Methods: Plasma samples from 95 overweight individuals consuming either 1.5 oz. of mixed tree nuts (MTNs, n = 56) or isocaloric pretzels (n = 39) daily for 12 weeks were analyzed. Nutritional data were collected at baseline and week 12 through dietary recall using the Automated Self-Administered 24 h Dietary Assessment Tool (ASA24), and the overall diet quality was assessed via the Healthy Eating Index (HEI) score. TMAO levels were determined and analyzed using linear mixed-effect models, adjusting for covariates. Wilcoxon signed-rank tests compared baseline and week 12 TMAO and weight. Multiple linear regression identified baseline predictors of TMAO. Results: Baseline demographics, anthropometric measures, HEI scores, and dietary choline intake were similar between the MTN and pretzel groups. A significant positive association was observed between baseline dietary choline and plasma TMAO levels (p = 0.012). The 12-week hypocaloric diet led to significant weight reduction in both groups (p < 0.01), but the magnitude of weight loss did not differ significantly between the MTN (−3.47 lbs) and pretzel (−4.25 lbs) groups (p = 0.18). Plasma TMAO levels decreased significantly in both groups (p < 0.01), but the between-group difference in reduction was not significant. (MTNs: −0.34 vs. pretzels: −0.37; p = 0.43). HEI scores and dietary choline intake remained unchanged, with no significant time–intervention interaction. Participants with low baseline HEI scores (≤53.72) had a more pronounced reduction in TMAO levels in the MTN group compared to the pretzel group (MTN: −0.54 vs. pretzel: −0.23; p = 0.045) over 12 weeks, despite similar weight loss. This difference was not observed in participants with higher HEI scores. Conclusions: The 12-week hypocaloric diet reduced body weight and plasma TMAO levels similarly in both MTN and pretzel groups. Participants with lower dietary quality saw a greater reduction in TMAO levels in the MTN group, suggesting MTNs may better modulate TMAO levels, especially for those with poorer baseline diets. Full article

Objective: Eggs are a valuable source of nutrients and bioactive compounds that may influence the gastrointestinal tract by modulating the microbiome, promoting the production of gastrointestinal-related metabolites, and mediating inflammation. Limited human studies have explored the effects of whole egg intake on indices of gastrointestinal health. This systematic literature review aimed to synthesise research investigating the impact of whole egg consumption on markers of gastrointestinal health. Methods: Five databases were searched from inception until July 2024. Studies were included if they examined the link between whole egg consumption and gastrointestinal markers, including symptoms, gut microbiome composition, inflammation, colonic fermentation, and egg-derived metabolites such as trimethylamine N-oxide (TMAO) in healthy adults. Two reviewers independently conducted title and abstract and full-text screening, with conflicts resolved by a third reviewer. Similarly, two authors conducted data extraction, which was verified by a third. A risk of bias assessment was conducted using validated tools. Random effects meta-analyses were performed to summarise the effect of egg consumption on TMAO, choline, and C-reactive protein (CRP). Results: Twenty-two studies were included in a narrative synthesis and ten in the meta-analyses. Nine were randomised controlled trials (RCTs), three were non-randomised intervention trials, eight were cross-sectional, and two were prospective cohort studies. Meta-analyses indicated that egg consumption did not impact plasma TMAO (n = 6, p = 0.22) or CRP (n = 3, p = 0.45) concentrations but did increase plasma choline (n = 5, p < 0.001) in the short term (≤4 weeks). Four studies found correlations between habitual egg consumption and specific gut bacteria, although results varied as egg consumption was both positively and negatively associated with butyrate-producing genera. Conclusions: This review found conflicting results regarding egg consumption and most gastrointestinal outcomes, highlighting that future studies are needed to explore links between habitual egg intake and plasma TMAO, microbial diversity, and inflammation (PROSPERO registration: 408532). Full article

Seafood, especially marine fish, is highly prone to spoilage during processing, transportation, and storage. It releases pungent trimethylamine (TMA) gas, which severely affects food quality and safety. Metal–oxide–semiconductor (MOS) gas sensors for TMA detection offer a rapid, convenient, and accurate method for assessing fish freshness. Indium oxide (In₂O₃) has shown potential as an effective sensing material for the detection of TMA. In this work, one-dimensional In₂O₃ nanowires with different grain sizes and levels of crystallinity were synthetized using the electrospinning technique and underwent different thermal calcination processes. Gas-sensing tests showed that the In₂O₃–3 °C/min–500 °C gas sensor exhibited an outstanding performance, including a high response (R_a/R_g = 47.0) to 100 ppm TMA, a short response time (6 s), a low limit of detection (LOD, 0.0392 ppm), and an excellent long-term stability. Furthermore, the sensor showed promising experimental results in monitoring the freshness of Larimichthys crocea (L. crocea). By analyzing the relationship between the grain size and crystallinity of the In₂O₃ samples, a mechanism for the enhanced gas-sensing performance was proposed. This work provides a novel strategy for designing and fabricating gas sensors for TMA detection and highlights their potential for broad applications in real-time fish freshness monitoring. Full article