Search Results (5,074)

Bifidobacterium adolescentis is prevalent in the gastrointestinal tract of healthy humans, and significantly influences host health. Recent studies have predominantly investigated the probiotic characteristics of individual strains and their specific metabolic roles, whereas analyses at the population genome level have been limited to date. This study conducted a comparative genomics analysis of 543 B. adolescentis genomes to explore genetic background variations and functional gene differences across geographically diverse populations. The results revealed significant differences in genome size and GC content among populations from Asia, Europe, and North America (p < 0.05). The pan-gene exhibited an open structure, reflecting the substantial genetic diversity within B. adolescentis. Functional annotation demonstrated that B. adolescentis possesses numerous protein-coding genes and abundant carbohydrate-active enzymes (CAZys) implicated in carbohydrate degradation and transformation. Population-specific CAZys were identified, suggesting adaptive evolution driven by distinct regional dietary patterns. Full article

Background: Clinical outcomes among older adults hospitalized with heart failure with preserved ejection fraction (HFpEF) in the setting of metabolically healthy obesity (MHO) remain insufficiently explored. This study aimed to evaluate whether MHO status is associated with different rates of major adverse cardiac and cerebrovascular events (MACCEs) during HFpEF-related hospitalizations compared to patients without MHO. Methods: Data from the 2019 National Inpatient Sample (NIS) database was analyzed using relevant ICD-10 codes to identify HFpEF admissions in older adults. Propensity score matching (1:1) was applied to generate balanced cohorts of patients with and without MHO. Multivariable adjustments were performed to assess primary outcomes, including MACCEs, all-cause mortality (ACM), acute myocardial infarction (AMI), dysrhythmia, cardiac arrest (CA), and stroke. Statistical significance was set at p < 0.05. Results: Each MHO cohort included 22,405 patients with a median age of 75 years. The MHO+ group demonstrated a significantly higher risk of dysrhythmia (OR 1.32, 95% CI 1.21–1.43, p < 0.001). Interestingly, an “obesity paradox” was observed, as the MHO+ cohort had lower odds of MACCEs (OR 0.70, 95% CI 0.61–0.81, p < 0.001), ACM (OR 0.66, 95% CI 0.54–0.82, p < 0.001), and AMI (OR 0.71, 95% CI 0.59–0.86, p = 0.001) compared to MHO−. No significant differences were found for CA or stroke between the groups. Conclusions: Although the MHO+ group had an elevated risk of dysrhythmia, they exhibited more favorable outcomes in terms of MACCEs, ACM, and AMI—supporting the concept of an “obesity paradox.” Further research is needed to better understand the role of MHO as a comorbid condition in patients with HFpEF. Full article

Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy controls. To our knowledge, the correlation between serum LPC species levels and measures of inflammation, as well as their potential as markers for monitoring IBD activity, has not yet been investigated. Methods: Thirteen LPC species, varying in acyl chain length and number of double bonds, were measured in the serum of 16 controls and the serum of 57 patients with IBD. Associations with C-reactive protein (CRP) and fecal calprotectin levels as markers of IBD severity were assessed. Results: Serum levels of LPC species did not differ between the healthy controls and the entire patient cohort. In patients with IBD, serum levels of LPC 16:1, 18:0, 18:3, 20:3, and 20:5, as well as total LPC concentrations, showed inverse correlations with both CRP and fecal calprotectin levels, indicating an association with inflammatory activity. Nine LPC species were significantly reduced in patients with high fecal calprotectin compared to those with low values. LPC species with 22 carbon atoms and 4 to 6 double bonds were not related to disease activity. Stool consistency and gastrointestinal symptoms did not influence serum LPC profiles. Corticosteroid treatment was associated with lower serum LPC 20:3 and 22:5 levels, while mesalazine, anti-TNF, and anti-IL-12/23 therapies had no significant impact on LPC concentrations. There was a strong positive correlation between LPC species containing 15 to 18 carbon atoms and serum cholesterol, triglycerides, and phosphatidylcholine levels. However, there was no correlation with markers of liver disease. Conclusions: Shorter-chain LPC species are reduced in patients with active IBD and reflect underlying hypolipidemia. While these lipid alterations provide insight into IBD-associated metabolic changes, they appear unsuitable as diagnostic or disease monitoring biomarkers. Full article

A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose and low-grade inflammation in overweight and obese subjects in a clinical trial. The aim of this study was to explore, for the first time, health-beneficial gene expression other than Glo1 induced by tRES+HESP in human endothelial cells and fibroblasts in primary culture and HepG2 hepatoma cell line and activity of cis-resveratrol (cRES) as a Glo1 inducer. We measured antioxidant response element-linked gene expression in these cells in response to 5 µM tRES+HESP by the NanoString method. tRES+HESP increases gene expression linked to the prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. The median effective concentration of tRES was ninefold lower than cRES in the Glo1 inducer luciferase reporter assay. The GlucoRegulate supplement provides a new treatment option for the prevention of type 2 diabetes and metabolic dysfunction–associated steatotic liver disease and supports healthy aging. Full article

Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. While its pharmacological effects are well known, the broader metabolic impact and potential mechanisms underlying improved clinical outcomes remain underexplored. Untargeted metabolomics, which profiles the metabolome without prior selection, is an emerging tool in clinical pharmacology for elucidating drug-induced metabolic changes. In this study, untargeted metabolomics was applied to investigate metabolic changes following a single oral dose of etodolac in healthy male volunteers. By analyzing serial blood samples over time, we identified endogenous metabolites whose concentrations were positively or inversely associated with the drug’s plasma levels. This approach provides a window into both therapeutic pathways and potential off-target effects, offering a promising strategy for early-stage drug evaluation and multi-target discovery using minimal human exposure. Methods: Thirty healthy participants received a 400 mg dose of Etodolac. Plasma samples were collected at five time points: pre-dose, before Cmax, at Cmax, after Cmax, and 36 h post-dose (n = 150). Samples underwent LC/MS-based untargeted metabolomics profiling and pharmacokinetic analysis. A total of 997 metabolites were significantly dysregulated between the pre-dose and Cmax time points, with 875 upregulated and 122 downregulated. Among these, 80 human endogenous metabolites were identified as being influenced by Etodolac. Results: A total of 17 metabolites exhibited time-dependent changes closely aligned with Etodolac’s pharmacokinetic profile, while 27 displayed inverse trends. Conclusions: Etodolac influences various metabolic pathways, including arachidonic acid metabolism, sphingolipid metabolism, and the biosynthesis of unsaturated fatty acids. These selective metabolic alterations complement its COX-2 inhibition and may contribute to its anti-inflammatory effects. This study provides new insights into Etodolac’s metabolic impact under healthy conditions and may inform future therapeutic strategies targeting inflammation. Full article

Aging, a progressive and time-dependent decline in physiological functions, is driven by interconnected hallmarks, among which mitochondrial dysfunction plays a central role. Mitochondria not only regulate energy production but also play key roles in other cellular processes, including ROS generation, apoptosis, and metabolic signaling—all of which decline with aging. Polyphenols are a diverse group of natural compounds found in fruits, vegetables, tea, and wine; they emerged as promising anti-aging agents due to their ability to modulate several hallmarks of aging, particularly mitochondrial dysfunction. This review explores how various polyphenolic classes influence mitochondrial function and mitigate aging-related decline. These natural compounds have been shown to reduce oxidative stress, increase energy production, and help maintain normal mitochondrial structure. Moreover, in vitro and in vivo studies suggest that polyphenols can delay signs of aging and improve physical and cognitive functions. Overall, polyphenols show great potential to promote healthy aging and even delay the decline in physiological functions by protecting and enhancing mitochondrial health. Full article

Background/Objectives: The association between chronic kidney disease (CKD) and body size phenotypes in metabolically diverse but apparently healthy adult populations remains inadequately understood. This study investigated the association between CKD and body size phenotypes in a nationally representative sample of healthy Korean adults. Methods: Data from 8227 participants in the 2019–2021 Korean National Health and Nutrition Examination Survey were analyzed. Participants were categorized into four body size phenotypes by combining BMI status (normal weight or obese) with metabolic health status (healthy or abnormal)—MHNW (Metabolically Healthy Normal Weight), MANW (Metabolically Abnormal Normal Weight), MHO (Metabolically Healthy Obese), or MAO (Metabolically Abnormal Obese). CKD was defined based on the urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR). To assess the association between CKD and body size phenotypes, multivariable logistic regression analyses were performed. Results: CKD prevalence was 4.4%. MANW and MAO made up 12.6% and 26.4% of the CKD group, compared to 5.0% and 13.2% of the non-CKD group. CKD prevalence by phenotype was observed as follows: MHNW, 3.2%; MANW, 10.5%; MHO, 4.0%; and MAO, 8.5%. CKD odds were highest in the MAO group (OR: 3.770, 95% CI: 2.648–5.367), followed by the MANW (OR: 2.492, 95% CI: 1.547–4.016) and MHO (OR: 1.974, 95% CI: 1.358–2.870) groups. MAO individuals carried a higher CKD risk than MHO individuals (OR: 1.897, 95% CI: 1.221–2.945). Conclusions: Among apparently healthy adults, body size phenotypes—particularly those with metabolic abnormalities—were significantly associated with the presence of CKD. These findings highlight the need to assess both metabolic health and body composition for effective CKD prevention and management. Full article

Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, functional, and resistance profiling to evaluate the gut microbiota of women with CD on a GFD. Methods: To evaluate the long-term impact of a GFD, this study analyzed the gut microbiota of 10 women with CD on a GFD for over a year compared to 10 healthy controls with unrestricted diets. Taxonomic diversity (16S rRNA gene sequencing and the analysis of α and β-diversity), metabolic functionality (Biolog EcoPlates^®), and antibiotic resistance profiles (Cenoantibiogram) were assessed. Results: Metagenomic analysis revealed no significant differences in taxonomic diversity but highlighted variations in the abundance of specific bacterial genera. Women with CD showed increased proportions of Bacteroides, Streptococcus, and Clostridium, associated with inflammation, but also elevated levels of beneficial genera such as Roseburia, Oxalobacter, and Paraprevotella. Despite no significant differences in metabolic diversity, higher minimum inhibitory concentrations (MICs) in women in the healthy control group suggest that dietary substrates in unrestricted diets may promote the proliferation of fast-growing bacteria capable of rapidly developing and disseminating antibiotic resistance mechanisms. Conclusions: These findings indicate that prolonged adherence to a GFD in CD supports remission of gut dysbiosis, enhances microbiota functionality, and may reduce the risk of antibiotic resistance, emphasizing the importance of dietary management in CD. Full article

Background/Objectives: Conventional ketogenic diets, although effective for weight loss, often contain high total and saturated fat intake, which leads to increased low-density lipoprotein cholesterol (LDL-C). Thus, the Healthy Ketogenic Diet (HKD) was developed to address these concerns. It emphasizes calorie restriction, limiting net carbohydrate intake to 50 g per day, prioritizing unsaturated fats, and reducing saturated fat intake. However, adherence to the HKD remains a challenge in urban, time-constrained environments. Therefore, this pilot randomized controlled trial aimed to investigate the effects of Healthy Ketogenic Diet Ready-To-Eat (HKD-RTE) meals (provided for the first month only) versus HKD alone on weight loss and metabolic parameters among overweight adults. Methods: Multi-ethnic Asian adults (n = 50) with a body mass index (BMI) ≥ 27.5 kg/m² were randomized into the HKD-RTE group (n = 24) and the HKD group (n = 26). Both groups followed the HKD for six months, with the HKD-RTE group receiving HKD-RTE meals during the first month. Five in-person workshops and mobile health coaching through the Nutritionist Buddy Keto app helped to facilitate dietary adherence. The primary outcome was the change in body weight at 6 months. Linear regression was performed on the change from baseline for each continuous outcome, adjusting for demographics and relevant covariates. Logistic regression was performed on binary weight loss ≥ 5%, adjusting for demographics and relevant covariates. Results: In the HKD group, participants’ adherence to the 50 g net carbohydrate target was 15 days, while that in the HKD-RTE group was 19 days over a period of 30 days. Participants’ adherence to calorie targets was 21 days in the HKD group and 23 days in the HKD-RTE. The average compliance with the HKD-RTE meals provided in the HKD-RTE group was 55%. The HKD-RTE group experienced a greater percentage weight loss at 1 month (−4.8 ± 3.0% vs. −1.8 ± 6.2%), although this was not statistically significant. This trend continued up to 6 months, with the HKD-RTE group showing a greater percentage weight reduction (−8.6 ± 6.8% vs. −3.9 ± 8.6%; p = 0.092). At 6 months, the HKD-RTE group had a greater reduction in total cholesterol (−0.54 ± 0.76 mmol/L vs. −0.05 ± 0.56 mmol/L; p = 0.283) and LDL-C (−0.43 ± 0.67 mmol/L vs. −0.03 ± 0.52 mmol/L; p = 0.374) compared to the HKD group. Additionally, the HKD-RTE group exhibited greater reductions in systolic blood pressure (−8.3 ± 9.7 mmHg vs. −5.3 ± 11.0 mmHg), diastolic blood pressure (−7.7 ± 8.8 mmHg vs. −2.0 ± 7.0 mmHg), and HbA1c (−0.3 ± 0.5% vs. −0.1 ± 0.4%) than the HKD group (not statistically significant for any). Conclusions: Both HKD-RTE and HKD led to weight loss and improved metabolic profiles. The HKD-RTE group tended to show more favorable outcomes. Short-term HKD-RTE meal provision may enhance initial weight loss, with sustained long-term effects. Full article

Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population remain limited. Methods: A single-center, prospective observational study included 100 children aged 4–18 years, with a comparable number of girls and boys. Among them, 72 had IBD (27 CD, 45 UC) and 28 were healthy controls. Anthropometric, biochemical, and densitometric assessments were performed, including serum levels of RANKL and OPG, and markers of inflammation and bone turnover. Results: Children with CD had significantly lower height and weight percentiles compared to UC and controls. Serum RANKL and the RANKL/OPG ratio were significantly elevated in IBD patients, particularly in CD (p < 0.01). Total body BMD Z-scores were lower in IBD compared to controls (p = 0.03). Low BMD was found in 14.7% of UC and 26.3% of CD patients. In both groups, over 30% had values in the “gray zone” (−1.0 to −2.0). A positive correlation was observed between height and weight and bone density (p < 0.01). Higher OPG was associated with lower body weight (p < 0.001), while increased RANKL correlated with osteocalcin (p = 0.03). Patients receiving biological therapy had significantly lower BMD. Conclusions: Pediatric IBD is associated with significant alterations in the RANKL/OPG axis and reduced bone density. These findings support early screening and suggest RANKL/OPG as a potential biomarker of skeletal health. Full article

Cholesterol accumulation plays a significant role in the pathogenesis of metabolic-dysfunction-associated steatotic liver disease (MASLD), yet changes in cholesterol homeostasis in MASLD remain insufficiently investigated. This study aimed to examine alterations in cholesterol synthesis and absorption by measuring plasma levels of endogenous cholesterol precursors (as markers of synthesis) and phytosterols (as indicators of absorption). A total of 124 MASLD patients and 43 healthy individuals were included. Our results showed higher plasma concentrations of lathosterol in the MASLD group (p = 0.006), in parallel with comparable concentrations of desmosterol (p = 0.472) and all analyzed phytosterols in both groups. Correlation analysis showed that both lathosterol and desmosterol were positively associated with non-invasive hepatic steatosis indices: FLI, HSI, and TyG index (p < 0.01, p < 0.01, and p < 0.05, respectively). Multivariate linear regression further confirmed that these synthesis markers remained significant predictors of FLI (p = 0.010), HSI (p = 0.013), and TyG index (p = 0.002), even after adjusting for other relevant variables. These findings indicate that MASLD is associated with a shift in cholesterol homeostasis towards enhanced endogenous cholesterol synthesis. Full article

Hydrogen sulfide (H₂S) can be produced from the metabolism of foods containing sulfur in the gastrointestinal tract (GIT). At low doses, H₂S regulates the gut microbial community and supports GIT health, but depending on dose, age, and individual health conditions, it may also contribute to inflammatory responses and gut barrier dysfunction. Controlling H₂S production in the GIT is important for maintaining a healthy gut microbiome. However, research on this subject is limited due to the gaseous nature of the chemical and the difficulty of accessing the GIT in situ. In the present ex vivo experiment, we used a single-dose sodium sulfide preparation (SSP) as a H₂S precursor to test the effect of H₂S on the human gut microbiome across different age groups, including breastfed infants, toddlers, adults, and older adults. Metagenomic sequencing and metabolite measurements revealed that the development of the gut microbial community and the production of short-chain fatty-acids (SCFAs) were age-dependent; that the infant and the older adult groups were more sensitive to SSP exposure; that exogeneous SSP suppressed SCFA production across all age groups, except for butyrate in the older adult group, suggesting that H₂S selectively favors specific gut microbial processes. Full article

Background: Metabolic syndrome (MetS) is a complex clinical condition characterized by the coexistence of interrelated metabolic abnormalities that significantly increase the risk of cardiovascular diseases and type 2 diabetes mellitus. Endocan—an endothelial cell-specific molecule—is considered a biomarker of endothelial dysfunction and inflammation. This study aimed to evaluate the relationship between serum endocan levels and the severity of MetS, assessed using the MetS-Z score. Methods: This study included 120 patients with MetS and 50 healthy controls. MetS was diagnosed according to the NCEP-ATP III criteria. MetS-Z scores were calculated using the MetS Severity Calculator. Serum levels of endocan, sICAM-1, and sVCAM-1 were measured using the ELISA method. Results: Serum levels of endocan, sICAM-1, and sVCAM-1 were significantly higher in the MetS group compared to the control group (all p < 0.001). When the MetS group was divided into tertiles based on MetS-Z scores, stepwise and statistically significant increases were observed in the levels of endocan and other endothelial markers from the lowest to highest tertile (p < 0.0001). Correlation analysis revealed a strong positive association between the MetS-Z score and serum endocan levels (r = 0.584, p < 0.0001). ROC curve analysis showed that endocan has high diagnostic accuracy for identifying MetS (AUC = 0.967, p = 0.0001), with a cutoff value of >88.0 ng/L. Conclusions: Circulating levels of endocan were significantly increased in MetS and were associated with the severity of MetS, suggesting that endocan may play a role in the cellular response to endothelial dysfunction-related injury in patients with MetS. Full article

Background: Charcot–Marie–Tooth (CMT) is a group of inherited diseases impairing the peripheral nervous system. CMT originates from genetic variants that affect proteins fundamental for the myelination of peripheral nerves and survival. Moreover, environmental and humoral factors can impact disease development and evolution. Currently, no therapy is available. Metabolomics is an emerging field of biomedical research that enables the development of novel biomarkers for neurodegenerative diseases by targeting metabolic pathways or metabolites. This study aimed to evaluate the metabolomics profile of CMT disease by comparing patients with healthy individuals. Methods: A total of 22 CMT patients (CMT) were included in this study and were demographically matched with 26 healthy individuals (C). Serum samples were analyzed through Nuclear Magnetic Resonance spectroscopy, and multivariate and univariate statistical analyses were subsequently applied. Results: A supervised model showed a clear separation (R²X = 0.3; R²Y = 0.7; Q² = 0.4; p-value = 0.0004) between the two classes of subjects, and nine metabolites were found to be significantly different (2-hydroxybutyrate, 3-hydroxybutyrate, 3-methyl-2-oxovalerate, choline, citrate, glutamate, isoleucine, lysine, and methyl succinate). The combined ROC curve showed an AUC of 0.94 (CI: 0.9–1). Additional altered metabolic pathways were also identified within the disease context. Conclusion: This study represents a promising starting point, demonstrating the efficacy of metabolomics in evaluating CMT patients and identifying novel potential disease biomarkers. Full article

Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota–gut–brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates whether FMT is feasible and improves cognition in adults with irritable bowel syndrome (IBS). Participants receive a single dose of FMT or placebo via rectal retention enema. Cognitive performance is the primary outcome, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include IBS symptom severity and mood. Tertiary outcomes include microbiome composition and plasma biomarkers related to inflammation, short-chain fatty acids, and tryptophan metabolism. Outcomes are assessed at baseline and at one, three, six, and twelve months following treatment. We hypothesise that FMT will lead to greater improvements in cognitive performance than placebo, with benefits extending beyond practice effects, emerging at one month and persisting in the long term. The findings will contribute to evaluating the safety and efficacy of FMT and enhance our understanding of gut–brain interactions. Full article