Metabolites[JOURNAL]
Sun
200 papers
Age-Specific Ex Vivo Modulation of Gut-Brain Axis-Associated Metabolites by Galacto-Oligosaccharides and Nutrient Blends in Early Childhood.
Ferrier L, Dogra SK, Vu LD … +5 more , Kanellopoulos AK, Poppe J, Biehl L, Baudot A, Van den Abbeele P
Metabolites · 2026 Apr · PMID 42042900 · Full text
: Gut microbiome-derived metabolites, particularly short-chain fatty acids (SCFA) and tryptophan derivatives, are central mediators of the gut-brain axis. This ex vivo study assessed how nutritional interventions impact...
: Gut microbiome-derived metabolites, particularly short-chain fatty acids (SCFA) and tryptophan derivatives, are central mediators of the gut-brain axis. This ex vivo study assessed how nutritional interventions impact such metabolites during early life, a critical period for neurodevelopment. : The effects of galacto-oligosaccharides (GOS), nutrient blends (vitamins, minerals and amino acids) and their combinations were evaluated in the gut microbiomes of infants (2-4 months, = 6) and young children (2-3 years old, = 6) using the ex vivo SIFR technology. : Baseline microbiome composition was age-dependent, with infants displaying lower α-diversity and greater interpersonal variability. After ex vivo incubation, nutrient blends increased the propionate/butyrate ratio and branched-chain fatty acids in young children and elevated several B-vitamins and amino acid-derived metabolites, including indole-3-carboxaldehyde, imidazoleacetic acid and pipecolinic acid. Combining nutrient blends with GOS exhibited potential synergistic effects on propionate (infants) and 2-hydroxyisocaproic acid (HICA, both age groups). GOS strongly stimulated and increased metabolites linked to bifidobacterial metabolism like acetate, HICA, N-acetylated amino acids, aromatic lactic acids and acetylagmatine; in young children, butyrate and γ-aminobutyric acid (GABA) also increased. : Combinations of GOS with nutrient blends impacted microbiome-derived metabolites associated with the gut-brain axis, with potential synergistic increases of metabolites with emerging roles in neurodevelopment, including GABA, acetylagmatine and HICA. Despite shared bifidogenic effects, differences between age groups indicate that microbiome maturity may influence responses to nutritional intervention. Future clinical studies are needed to determine whether these metabolite changes translate into neurodevelopmental benefits in vivo.
Citrus Peels in Health Foods: A Case Study of Pulp-Free Japanese-Grown Bushukan ( var. ).
Nakahigashi J, Kobayashi E
Metabolites · 2026 Apr · PMID 42042899 · Full text
Citrus peels are widely utilized as functional ingredients in health foods; however, their functional value is often assumed based on botanical classification rather than verified chemical composition. Bushukan ( var. )...
Citrus peels are widely utilized as functional ingredients in health foods; however, their functional value is often assumed based on botanical classification rather than verified chemical composition. Bushukan ( var. ) was selected as it lacks developed edible pulp; consequently, the usable portion consists almost entirely of peel tissue, making it a suitable model for evaluating peel-specific functional components. This commentary highlights the importance of species- and origin-specific evaluation through a case study of Bushukan ( var. ) whole fruit powder cultivated in Japan. Dried whole-fruit powder samples of bushukan, prepared by freeze-drying and hot-air drying at 50 °C, were analyzed, and the contents of hesperidin and nobiletin were quantified using high-performance liquid chromatography (HPLC) following methanol reflux extraction. Hesperidin was detected at 75 mg/100 g under both drying conditions, whereas nobiletin was below the practical limit of quantification (approximately 1 mg/100 g). No reduction in hesperidin content was observed after drying at 50 °C. These levels were markedly lower than those reported for commonly used citrus peels, such as satsuma mandarin, in previous studies. This commentary demonstrates that Japanese-grown bushukan samples do not necessarily provide substantial levels of commonly expected citrus flavonoids. These findings underscore the need for species- and origin-specific compositional verification before the use of citrus peels as raw materials for health food applications, illustrating this need through a practical, cautionary case study.
Common Skin Diseases and Metabolic Syndrome: A Proinflammatory Chemokine Perspective.
Matwiejuk M, Myśliwiec H, Mikłosz A … +2 more , Chabowski A, Flisiak I
Metabolites · 2026 Apr · PMID 42042898 · Full text
Skin diseases frequently coexist with other disorders, such as metabolic syndrome, diabetes mellitus, depression, psoriatic arthritis, and cardiovascular disease. Altered levels of distinct chemokines, like CCL5/RANTES,...
Skin diseases frequently coexist with other disorders, such as metabolic syndrome, diabetes mellitus, depression, psoriatic arthritis, and cardiovascular disease. Altered levels of distinct chemokines, like CCL5/RANTES, CXCL12/SDF-1a, CCL7/MCP-3, CCL2/MCP-1, CXCL1/GROa, and the eotaxin family, contribute to the development and/or exacerbation of inflammation, which is a common feature of numerous skin diseases as well as metabolic syndrome. The pathological and molecular connections between chronic inflammatory skin diseases and metabolic syndrome are increasingly recognized as being driven by shared inflammatory pathways, oxidative stress, and adipokine dysregulation. While systemic inflammation acts as a common thread, the precise mechanisms for some conditions remain partially understood. Nevertheless, the exact pathological and molecular connections between skin diseases (i.e., psoriasis, atopic dermatitis, pemphigus vulgaris, acute and chronic spontaneous urticaria, bullous pemphigoid, squamous cell carcinoma, alopecia areata, systemic sclerosis, discoid lupus erythematosus, diffuse large B-cell lymphoma) and metabolic syndrome are not yet fully understood. This narrative review summarizes the robust association between various chronic inflammatory skin diseases and metabolic syndrome in the context of pro-inflammatory chemokines.
Evaluation of Nutritional, Antioxidant, Antidiabetic, and Antidyslipidemic Properties of Red Corn Tortillas Enriched with Leaves.
Tranquilino-Rodríguez E, Calderón-Téllez N, Virgen-Ortiz JJ … +4 more , Figueroa-Cárdenas JD, Zamora-Vega R, Rodiles-López JO, Martínez-Flores HE
Metabolites · 2026 Apr · PMID 42042897 · Full text
Metabolic diseases are increasingly associated with diets low in bioactive compounds. Native maize varieties possess functional potential; however, they remain underutilized. leaf flour (MF), rich in protein and polyphe...
Metabolic diseases are increasingly associated with diets low in bioactive compounds. Native maize varieties possess functional potential; however, they remain underutilized. leaf flour (MF), rich in protein and polyphenols, represents a promising functional ingredient. This study evaluated the incorporation of MF into red native corn tortillas and its effects on nutritional composition and antioxidant capacity, as well as assessed its hypoglycemic and hypolipidemic effects in Wistar rats. Tortillas were formulated with 5% MF. Nutritional composition was determined using standard AOAC methods, while bioactive compounds (total phenolics and flavonoids) and antioxidant activity were evaluated using Folin-Ciocalteu, aluminum chloride (AlCl) colorimetric, DPPH, and ABTS assays, respectively. Male Wistar rats (12 weeks old, with an approximate weight ofs 360 g; = 5/group) were fed the experimental diets for 21 days with either a standard diet, a high-fat diet, or high-fat diets supplemented with MF or MF-enriched tortillas. Serum glucose, triglycerides, total cholesterol, and HDL were measured using enzymatic colorimetric methods. Data were analyzed by ANOVA followed by Tukey's test ( < 0.05). MF incorporation increased protein (+19.85%), dietary fiber (+18.51%), and mineral content (+41.03%) compared to control tortillas. Total phenolics and flavonoids increased by 114.0% and 184.7%, respectively. Antioxidant activity improved significantly, as evidenced by reductions in IC values of 41.1% (DPPH) and 43.1% (ABTS). In vivo, MF-enriched tortillas reduced triglycerides by 68.4%, total cholesterol by 16.2%, and hepatic lipid accumulation by 31.8% compared to the high-fat diet group. Glucose levels showed a reduction of 8.5%, although not statistically significant ( > 0.05). The incorporation of MF into red corn tortillas significantly enhances their nutritional and functional properties. In vivo results also showed improvements in lipid profile and a non-significant reduction in glucose levels. These findings support the development of functional foods based on traditional staples with potential health benefits.
Serum Uric Acid as a Biomarker for Incident Type 2 Diabetes Mellitus: A 6-Year Cohort Study in Qatar.
Saeed A, Chawa Y, Kaspo S … +3 more , Ibrahim H, Al Adab A, Kalfah A
Metabolites · 2026 Apr · PMID 42042896 · Full text
BACKGROUND: Serum uric acid (SUA) may predict incident type 2 diabetes mellitus (T2DM), but longitudinal evidence from Middle Eastern populations remains limited. METHODS: We conducted a retrospective cohort study using...
BACKGROUND: Serum uric acid (SUA) may predict incident type 2 diabetes mellitus (T2DM), but longitudinal evidence from Middle Eastern populations remains limited. METHODS: We conducted a retrospective cohort study using electronic health records from Qatar's Primary Health Care Corporation over a six-year period (2018-2023). Adults aged ≥18 years with at least one valid serum uric acid (SUA) measurement and no prior diabetes at baseline were eligible. All eligible participants were retained; no propensity score matching was performed. Baseline SUA was defined at the first valid measurement, and repeated-measure exposures included current SUA, cumulative-average SUA, and landmark time-weighted average (TWA) SUA. Sex-specific SUA categories were low <208, normal 208-428, and high >428 µmol/L in males and low <149, normal 149-357, and high >357 µmol/L in females. Sex-stratified Cox models, restricted cubic spline analyses, prespecified sensitivity analyses, and complementary explainable boosting machine (EBM) models were used to evaluate associations with incident type 2 diabetes mellitus (T2DM). RESULTS: The cohort included 169,876 adults (85,361 males and 84,515 females) and 18,714 incident T2DM events. In fully adjusted baseline Cox models, high baseline SUA was associated with higher T2DM hazard in females (hazard ratio [HR]: 1.44; 95% CI: 1.36-1.53), whereas low baseline SUA was associated with higher hazard in males (HR: 1.60; 95% CI: 1.44-1.78), and high SUA was not. In women, positive SUA-T2DM associations persisted in time-varying and landmark analyses, including current high- versus- normal SUA (HR: 1.50; 95% CI: 1.41-1.58) and 2-measurement landmark TWA SUA per 1 mg/dL (HR: 1.17; 95% CI: 1.13-1.20). In men, unlagged whole-cohort analyses showed inverse continuous associations, but lagged and repeated-measure analyses shifted toward positive associations, including 365-day lagged high- versus- normal baseline SUA (HR: 1.19; 95% CI: 1.11-1.28) and 2-measurement landmark TWA SUA per 1 mg/dL (HR: 1.06; 95% CI: 1.03-1.09). Restricted cubic splines showed a steadily rising risk gradient in females above approximately 262 µmol/L and a J-shaped pattern in males, with the lowest risk near 374 µmol/L. In EBM models, TWA SUA ranked third in women and fifth in men in the 2-measurement landmark cohorts. CONCLUSIONS: In this large Qatar cohort, longitudinal SUA was associated with incident T2DM in a sex-specific manner, with consistent positive associations in females and exposure-definition-dependent patterns in males. Repeated SUA measurements may improve diabetes risk stratification, but causal and therapeutic implications require further study.
TMT Proteomics-Based Study of Proteins and Pathways Associated with β-Glucan Degradation in Barley Germination.
Huang J, Ning F, Zhang G
Metabolites · 2026 Apr · PMID 42042895 · Full text
: Zangqing '1127', a hull-less barley type recognized for its high β-glucan content, holds significant agricultural and nutritional potential. Nonetheless, the molecular mechanisms underlying the degradation of β-glucan...
: Zangqing '1127', a hull-less barley type recognized for its high β-glucan content, holds significant agricultural and nutritional potential. Nonetheless, the molecular mechanisms underlying the degradation of β-glucan during barley germination have yet to be thoroughly investigated. : This study sought to identify the key proteins and pathways involved in this process using quantitative proteomics. : Seeds of Zangqing '1127' were collected at 0, 24, and 96 h post germination, and TMT-based quantitative proteomics was used to analyze changes in the proteome. To annotate the functions of differentially expressed proteins (DEPs), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. : In total, 3230 unique proteins were identified, which included 610 DEPs during the germination phase. Enrichment analysis showed that these DEPs were primarily associated with key biological processes involved in β-glucan degradation, including cell wall modification, polysaccharide metabolism, and carbon metabolism. Five proteins exhibiting notably high expression levels were identified as potential regulatory candidates for this process. : These results enhance our comprehension of the proteomic dynamics associated with β-glucan degradation during barley germination and suggest new candidate targets for functional studies. This study provides deeper insight into the molecular mechanisms governing β-glucan metabolism, with potential implications for agricultural improvement and the nutritional quality of barley.
Association Between Psychological Distress and Sleep Quality in Children and Adolescents: A Cross-Sectional Study in Zhejiang, China.
Liang T, Zhuang Z, Wu L … +3 more , Li X, Chen Z, Xing M
Metabolites · 2026 Apr · PMID 42042894 · Full text
: Psychological distress has been increasingly recognized as an important determinant of sleep quality in children and adolescents. However, susceptible subgroups have not been clearly identified. This study aimed to exa...
: Psychological distress has been increasingly recognized as an important determinant of sleep quality in children and adolescents. However, susceptible subgroups have not been clearly identified. This study aimed to examine the associations between psychological distress and sleep quality in children and adolescents. : We conducted a cross-sectional study among 5771 school-aged children and adolescents (6-18 years) in Zhejiang Province. Psychological status was assessed using the Chinese version of the Depression Anxiety Stress Scale-21, and sleep quality was evaluated using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). Thyroid-related biomarkers were measured via chemiluminescence immunoassay. Associations between psychological distress and sleep quality were analyzed using generalized linear models. In addition, stratified analyses were performed to identify potentially susceptible subgroups by age, sex, and BMI-for-age z score. : Each one-point increase in depression, anxiety, and stress scores was associated with an increase in PSQI scores of 0.18 (95% CI: 0.16, 0.19), 0.20 (95% CI: 0.18, 0.21), and 0.20 (95% CI: 0.19, 0.22), respectively. Subgroup analyses showed that the associations were more pronounced among older children (age > 12 years) and pediatric females. Exploratory mediation analyses suggested a possible but very limited indirect role of T3 in the associations of depression, anxiety, and stress with sleep quality, with all estimated proportions mediated below 1%. : Psychological distress was significantly associated with poorer sleep quality in children and adolescents, particularly among older individuals and pediatric females. These findings highlight the importance of early identification and intervention for psychological distress to improve sleep health in younger populations. Further longitudinal studies are needed to clarify underlying mechanisms.
Personalizing Obesity Treatment: Real-World Comparison of a Very-Low-Calorie Ketogenic Diet Versus a Whole-Food Mediterranean Ketogenic Diet.
Masi D, Spizzichini ML, Colonnello E … +4 more , Vasquez Barahona D, Gnessi L, Gianfrilli D, Watanabe M
Metabolites · 2026 Apr · PMID 42042893 · Full text
Obesity is a chronic, relapsing disease in which lifestyle modification represents the cornerstone of treatment. Among dietary strategies, ketogenic diets can induce rapid weight loss, whereas the Mediterranean diet is a...
Obesity is a chronic, relapsing disease in which lifestyle modification represents the cornerstone of treatment. Among dietary strategies, ketogenic diets can induce rapid weight loss, whereas the Mediterranean diet is associated with established cardiometabolic benefits but typically produces slower weight reduction. Very-low-calorie ketogenic diets (VLCKDs) are effective for weight loss but are often limited by cost, reliance on meal replacements, and reduced long-term feasibility. This study aimed to evaluate whether a whole-food Mediterranean ketogenic diet with moderate caloric restriction (MedKD) could represent a feasible and effective alternative to VLCKD for weight loss and metabolic improvement in adults with obesity. This 3-month prospective, real-world study compared VLCKD and MedKD in adults with obesity attending a clinical nutrition program. The primary outcome was percentage weight loss. Secondary outcomes included changes in waist circumference, waist-to-height ratio, insulin resistance (HOMA-IR), lipid profile, kidney function, and treatment tolerability. Clinical and biochemical parameters were assessed at baseline and after the intervention. Group differences and time-by-group interactions were analyzed to evaluate changes over the study period. Sixty-two participants were enrolled, and 55 completed the study (27 VLCKD, 28 MedKD). Baseline characteristics were generally comparable, although the MedKD group had a higher prevalence of diabetes and higher baseline insulin resistance and triglyceride levels. Both dietary interventions resulted in substantial and comparable weight loss (approximately 15% of initial body weight), accompanied by significant reductions in waist circumference and waist-to-height ratio. Insulin resistance improved in both groups, with a greater reduction in HOMA-IR observed in the MedKD group (time × group = 0.031). Serum creatinine decreased in the VLCKD group and slightly increased in the MedKD group ( = 0.025). Changes in lipid profile were not significantly different between groups. No severe adverse events were reported. A whole-food Mediterranean ketogenic diet with moderate caloric restriction achieved weight loss and metabolic improvements comparable to those observed with VLCKD over three months. These findings suggest that MedKD may represent a feasible alternative to formula-based ketogenic programs, supporting more flexible and personalized dietary strategies in the clinical management of obesity.
New Insights into Dietary L-Glutamate and L-Aspartate Modulation of Hematology, Immune Responses, and Metabolite Profiles in Enterotoxigenic Challenged Piglets.
Wongchanla S, Park S, Sun S … +2 more , Ji P, Liu Y
Metabolites · 2026 Apr · PMID 42042892 · Full text
BACKGROUND/OBJECTIVES: L-glutamate (Glu) and L-aspartate (Asp) are key intermediates in nitrogen metabolism and tricarboxylic acid cycle activity, linking intestinal energy metabolism with immune function. This study inv...
BACKGROUND/OBJECTIVES: L-glutamate (Glu) and L-aspartate (Asp) are key intermediates in nitrogen metabolism and tricarboxylic acid cycle activity, linking intestinal energy metabolism with immune function. This study investigated how dietary Glu and Asp supplementation modulates immune responses and metabolic reprogramming in weaned pigs challenged with F18 enterotoxigenic (ETEC). METHODS: Forty-nine piglets (24 d old; 8.18 ± 1.54 kg body weight) were randomly assigned to seven treatments ( = 7/treatment): unchallenged control (NC), ETEC-challenged control (PC), 1% or 2% Glu, 1% or 2% Asp, and an antibiotic control. The experiment was conducted from d -7 to d 14 post-inoculation (PI). Hematological indices, serum biomarkers, intestinal cytokine gene expression, and untargeted metabolomic profiling of serum, ileal mucosa, and ileal digesta were evaluated. RESULTS: On day 2 PI, 1% Glu reduced the neutrophil-to-lymphocyte ratio, whereas 2% Asp showed an elevated ratio. Supplementation of 1% Asp increased serum total protein on d 2 and d 5 PI. On d 14 PI, 1% Glu enhanced jejunal and expression, while 2% Asp reduced jejunal expression compared with PC. Ileal expression increased with 1% Glu and 2% Asp, whereas jejunal expression decreased with 2% Glu and 2% Asp. Untargeted metabolomics revealed distinct treatment-dependent separations. Differential metabolite profiling and pathway enrichment analyses demonstrated coordinated alterations in amino acid metabolism, purine metabolism, lipid metabolism, and energy-related pathways across serum and intestinal compartments. CONCLUSIONS: Collectively, Glu and Asp supplementation reshaped host metabolic networks during ETEC challenge, indicating their roles in modulating metabolic adaptation and intestinal immune-metabolic crosstalk under enteric stress.
Waist-to-Height Ratio as a Simple Anthropometric Marker for Identifying Individuals at High Risk of MASLD: A Large Population-Based Analysis Using the Fatty Liver Index.
López-González ÁA, Tárraga López PJ, Piña Dabreu MS … +3 more , Rodas Cañellas L, Busquets-Cortés C, Ramírez-Manent JI
Metabolites · 2026 Apr · PMID 42042891 · Full text
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and represents a major component of the global burden of metabolic disorders. Simple anthrop...
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and represents a major component of the global burden of metabolic disorders. Simple anthropometric markers capable of identifying individuals at increased risk of hepatic steatosis are of considerable interest for population-level screening. METHODS: In this cross-sectional population-based study, we evaluated the performance of waist-to-height ratio (WtHR) for identifying individuals with a high Fatty Liver Index (FLI ≥ 60), a widely used surrogate marker of hepatic steatosis. The study included 146,318 adult participants with available anthropometric and biochemical data. Discriminatory performance was assessed using receiver operating characteristic (ROC) curve analysis. Optimal WtHR thresholds were determined using the Youden index. Associations between WtHR and high FLI were evaluated using age-adjusted logistic regression models. Non-linear relationships were explored using restricted cubic spline models. Additional analyses included a comparison with body mass index (BMI) and waist circumference, decision curve analysis, and subgroup analyses across age and BMI strata. RESULTS: The prevalence of high FLI in the study population was 18.1%. WtHR demonstrated excellent discriminatory performance, with area under the ROC curve (AUC) values of 0.908 (95% CI 0.906-0.910) in men and 0.972 (95% CI 0.971-0.974) in women. Optimal WtHR thresholds for identifying individuals with high FLI were 0.52 in men and 0.53 in women. Each 0.01 increase in WtHR was strongly associated with higher odds of high FLI (OR 1.56 in men and 1.69 in women). Restricted cubic spline analysis demonstrated a non-linear relationship, with a marked increase in predicted probability of high FLI above WtHR values of approximately 0.50-0.52. WtHR showed discriminatory performance comparable to BMI and waist circumference and maintained strong associations with high FLI across age groups and BMI categories. CONCLUSIONS: Waist-to-height ratio is a simple anthropometric marker strongly associated with a high Fatty Liver Index in a large population-based cohort. Given its simplicity, low cost, and ease of calculation, WtHR may represent a practical screening indicator for identifying individuals at increased risk of MASLD-related phenotypes in both clinical practice and population health strategies.
Information-Content-Informed Kendall-Tau Correlation Methodology: Interpreting Missing Values in Metabolomics as Potentially Useful Information.
Flight RM, Bhatt PS, Moseley HNB
Metabolites · 2026 Apr · PMID 42042890 · Full text
Almost all correlation measures currently available are unable to directly handle missing values. Typically, missing values are either ignored completely by removing them or are imputed and used in the calculation of the...
Almost all correlation measures currently available are unable to directly handle missing values. Typically, missing values are either ignored completely by removing them or are imputed and used in the calculation of the correlation coefficient. In either case, the correlation value will be impacted based on the perspective that the missing data represents no useful information. However, missing values occur in real datasets for a variety of reasons. In metabolomics datasets a major reason for missing values is that a specific measurable phenomenon falls below the detection limits of the analytical instrumentation (left-censored values). These missing data are not missing at random, but represent potentially useful information by virtue of their "missingness" at one end of the data distribution. To include this information due to left-censored missingness, we propose the information-content-informed Kendall-tau (ICI-Kt) methodology. We develop a statistical test and then show that most missing values in metabolomics datasets are the result of left-censorship. Next, we show how left-censored missing values can be included within the definition of the Kendall-tau correlation coefficient, and how that inclusion leads to an interpretation of information being added to the correlation. We also implement calculations for additional measures of theoretical maxima and pairwise completeness that add further layers of information interpretation in the methodology. Using both simulated and over 700 experimental data sets from the Metabolomics Workbench, we demonstrate that the ICI-Kt methodology allows for the inclusion of left-censored missing data values as interpretable information, enabling both improved determination of outlier samples and improved feature-feature network construction. We provide explicitly parallel implementations in both R and Python that allow fast calculations of all the variables used when applying the ICI-Kt methodology on large numbers of samples. The ICI-Kt methods are available as an R package and Python module on GitHub.
Does Capillary or Intravenous Collection of Dried Blood Spots Affect the Results of Amino Acid and Acylcarnitine Profile Studied with Tandem Mass Spectrometry?
Kadıoğlu Yılmaz B, Sivrikaya A, Ünlü A
Metabolites · 2026 Apr · PMID 42042889 · Full text
This study investigated whether capillary and intravenous sampling affect acylcarnitine and amino acid profile results analyzed by tandem mass spectrometry. The study included 120 patients either diagnosed with an inher...
This study investigated whether capillary and intravenous sampling affect acylcarnitine and amino acid profile results analyzed by tandem mass spectrometry. The study included 120 patients either diagnosed with an inherited metabolic disease or undergoing evaluation for a suspected metabolic disorder at the Department of Pediatric Nutrition and Metabolism, Selçuk University Faculty of Medicine. Paired capillary and intravenous blood samples were collected simultaneously, applied to filter paper, and analyzed by LC-MS/MS to determine acylcarnitine and amino acid profiles. Significant differences were observed between capillary and intravenous samples for several acylcarnitines, including C0, C2, C8, C8.1, C10, C10.1, C14.1, C16, and C18.1 ( < 0.05). In the amino acid profile, arginine, aspartic acid, citrulline, glutamic acid, glycine, leucine + isoleucine, methionine, tyrosine, and the methionine/phenylalanine ratio differed significantly between sampling methods ( < 0.05). Despite these differences, Cohen's kappa analysis showed high agreement between capillary and venous samples for most parameters (78.3-100%) when categorized as low, normal, or high based on reference ranges. Additionally, no significant discrepancies were found in key diagnostic parameters among patients with specific inherited metabolic diseases. Although certain acylcarnitine and amino acid levels differed between capillary and intravenous samples, overall diagnostic agreement was high. However, since the study group did not include any patients with fatty acid oxidation disorders, a separate confirmatory study is needed for this condition. Larger multicenter studies involving more patients and a wider range of metabolic disorders are needed to better understand the clinical impact of sampling method on dried blood spot analyses.
Association Between Chronotype and Cardiometabolic Risk in 1462 Adults from the General Population: Mediation Analysis of Body Fat Percentage and Waist-to-Height Ratio.
Iman Torres AJ, Vásquez Chumbe JP, Sifuentes Da Silva JA … +5 more , Ruiz-Paredes R, Alva Arévalo AG, Guerra Sangama W, Castillo-Paredes A, Narrea Vargas JJ
Metabolites · 2026 Apr · PMID 42042888 · Full text
Circadian misalignment has been proposed as a potential determinant of cardiometabolic risk. Chronotype, as an expression of individual circadian organization, has been associated with unfavorable metabolic profiles; how...
Circadian misalignment has been proposed as a potential determinant of cardiometabolic risk. Chronotype, as an expression of individual circadian organization, has been associated with unfavorable metabolic profiles; however, the role of total and central adiposity as potential mediating mechanisms in this relationship remains incompletely understood. This study aimed to analyze the association between chronotype and cardiometabolic risk in adults and to evaluate the potential mediating role of body fat percentage (BF%) and waist-to-height ratio (WHtR). An observational study was conducted in 1462 adults from the general population. Chronotype was assessed using the Morningness-Eveningness Questionnaire (MEQ), and cardiometabolic risk was evaluated using a continuous cardiometabolic risk score (CMRS) derived from waist circumference (WC), systolic blood pressure (SBP), triglycerides (TG), fasting blood glucose (FBG), and total cholesterol (TC). Multiple linear regression models adjusted for covariates were used to examine the association between chronotype and CMRS, and hierarchical regression was performed to estimate the incremental contribution of adiposity indicators. Mediation analysis was conducted using the PROCESS macro (Model 4) with 95% bootstrap confidence intervals. Chronotype was independently associated with CMRS after adjustment for covariates (β = 0.055; = 0.030), although the effect size and explained variance were small. In hierarchical regression analysis, the inclusion of chronotype explained a small but significant increase in CMRS variance (ΔR = 0.003; = 0.030). The addition of adiposity indicators significantly increased the explained variance (ΔR = 0.014; < 0.001), with WHtR emerging as the most relevant predictor in the final model. Bootstrap mediation analysis did not reveal significant indirect effects of BF% or WHtR on the relationship between chronotype and CMRS. In sensitivity analyses excluding waist circumference from the CMRS, the association between chronotype and cardiometabolic risk was no longer significant (β = -0.001; = 0.974). Chronotype showed a modest association with cardiometabolic risk in the primary analysis. However, sensitivity analyses indicated that this association may partly depend on the inclusion of waist circumference within the composite cardiometabolic risk score. These findings highlight the central role of abdominal adiposity in cardiometabolic health and suggest that the relationship between chronotype and cardiometabolic risk should be interpreted with caution.
Denatonium Benzoate, the Most Bitter Compound, Reduces Weight by Promoting Adipocyte Browning.
Niu Y, Shao J, Teng Y … +3 more , Zhang C, Xie X, Guo S
Metabolites · 2026 Apr · PMID 42042887 · Full text
OBJECTIVES: Obesity remains a global health challenge, and promoting white adipose tissue browning has emerged as a promising anti-obesity strategy. This study aimed to investigate the anti-obesity effects of denatonium...
OBJECTIVES: Obesity remains a global health challenge, and promoting white adipose tissue browning has emerged as a promising anti-obesity strategy. This study aimed to investigate the anti-obesity effects of denatonium benzoate (DB) and elucidate its underlying mechanisms. METHODS: In order to study the anti-obesity effects of DB and its mechanisms, we used in vivo and in vitro obesity models to study whether DB has anti-obesity effects by participating in fat browning. We investigated the role of DB in high-fat diet (HFD)-induced obese mice using 36 male animals (8 weeks old, 25 ± 2 g), and evaluated the expression of the adipogenic marker genes Fatty acid-binding protein 4 () and Peroxisome Proliferator-Activated Receptor gamma (); the thermogenic genes uncoupling protein 1 (), Transcription Factor A, Mitochondrial (), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (), and Adrenergic receptor beta 3 (); as well as the adipose browning marker genes Deiodinase, Iodothyronine, Type II (), PR domain containing 16 (), and Peroxisome Proliferator-Activated Receptor alpha () in 3T3-L1 cells and primary adipocytes with DB treatment. CONCLUSIONS: These results indicate that the anti-obesity effects of DB may be related to the browning of white fat, providing a novel potential candidate for anti-obesity drug development.
Towards Metabolomics-Guided Healthy and Anti-Aging Nutrition.
Lokhov PG, Balashova EE, Maslov DL … +3 more , Trifonova OP, Lokhov AP, Archakov AI
Metabolites · 2026 Apr · PMID 42042886 · Full text
: Metabolomic studies have generated extensive data on metabolic changes in aging and disease, yet translating this data into practical nutrition guidelines remains challenging. Recent analysis identified pathways common...
: Metabolomic studies have generated extensive data on metabolic changes in aging and disease, yet translating this data into practical nutrition guidelines remains challenging. Recent analysis identified pathways common to both processes, termed the metapathway. As a network, it features key central metabolites that most representatively reflect its state. The manageable number of these key metabolites provides a practical basis for translating complex metabolomic data into actionable nutritional information. We developed a conceptual framework for precision nutrition approach involving: (1) selecting an initial (baseline) diet with minimal impact on key metapathway metabolites, (2) defining dietary modifications using foods and supplements that are capable of elevating them, and (3) implementing mass spectrometry-based metabolome fingerprinting to assess individual responses. This capability was evaluated using blood plasma and dried blood spot samples. A promising precision nutrition was created, consisting of a selected baseline diet and its metabolomics-guided modification. The metabolic fingerprinting demonstrated the possibility of determining the diet outcome by identifying biological age change with an accuracy of 1 month. : The fully metabolomics-guided nutrition strategy has been developed and is ready for further human testing to validate its translational potential and health benefits.
A Pilot Serum Metabolomics Reveals Mitochondrial Dysfunction and Identifies Methylguanidine as a Potential Diagnostic Biomarker for ATAAD with Mesenteric Malperfusion Syndrome.
Wen J, Zheng W, Sun L … +5 more , Lu L, Lin Z, Chen L, Peng H, Wang Y
Metabolites · 2026 Apr · PMID 42042885 · Full text
BACKGROUND: Acute type A aortic dissection complicated by mesenteric malperfusion syndrome (ATAAD-MMPS) is a highly lethal emergency with diagnostic challenges due to rapid progression and non-specific symptoms. This pil...
BACKGROUND: Acute type A aortic dissection complicated by mesenteric malperfusion syndrome (ATAAD-MMPS) is a highly lethal emergency with diagnostic challenges due to rapid progression and non-specific symptoms. This pilot study aimed to characterize the serum metabolomic and lipidomic alterations specific to ATAAD-MMPS and identify potential early diagnostic biomarkers. METHODS: Serum samples from healthy controls, patients with uncomplicated ATAAD, and patients with ATAAD-MMPS were analyzed using targeted metabolomics and lipidomics. Multivariate statistical analyses were performed to discriminate between groups and identify differentially abundant metabolites and lipids. Pathway analysis was conducted to explore underlying pathological mechanisms. RESULTS: Metabolomic profiles clearly distinguished ATAAD-MMPS from uncomplicated ATAAD, whereas lipidomic changes were primarily associated with ATAAD itself rather than the presence of mesenteric malperfusion. Metabolic pathway analysis revealed significant perturbations in the citric acid cycle, suggesting mitochondrial involvement as a potential pathological feature. Notably, methylguanidine was uniquely and markedly elevated in the ATAAD-MMPS group, demonstrating potential diagnostic value in distinguishing this lethal complication from uncomplicated ATAAD in this exploratory cohort (AUC = 0.923). CONCLUSIONS: This pilot study identifies distinct metabolic signatures associated with mesenteric malperfusion in ATAAD, with mitochondrial metabolic perturbations emerging as a potential contributing mechanism. Methylguanidine represents a candidate early diagnostic biomarker for ATAAD-MMPS, warranting validation in larger prospective studies. These findings provide a foundation for improved diagnostic strategies for this devastating condition.
In Vitro/In Silico Potential of High-Yield Essential Oils for Management of Postharvest Fungi.
Pineda-Ríos JM, Ruiz-Aguilar DA, Morales-Galván Ó … +5 more , Arévalo-Galarza MLC, López-Romero RM, Ayala-Escobar V, Vázquez-Sánchez M, Salomé-Abarca LF
Metabolites · 2026 Mar · PMID 42042884 · Full text
: Microbial infections represent a major challenge in the food processing chain. Postharvest fungal control has historically relied on chemical control; however, their use is increasingly restricted due to environmental...
: Microbial infections represent a major challenge in the food processing chain. Postharvest fungal control has historically relied on chemical control; however, their use is increasingly restricted due to environmental and health risks. Therefore, the aim of this study was to evaluate the antifungal potential of essential oils obtained from high-yield plant species and characterize the potential mechanisms of action of their major volatiles, with the goal of proposing a prospective formulation for the control of postharvest fungi. : Cinnamon, rosemary, allspice, and Peruvian pepper essential oils were extracted by hydrodistillation, tested against and sp., and analyzed by gas chromatography-mass spectrometry. Finally, in silico bioactivity analyses were performed on the most abundant volatiles. : Cinnamon and rosemary produced the most effective oils against both fungal species. Cinnamaldehyde, cinnamyl acetate, eugenol, methyleugenol, (+)-2-bornanone, eucalyptol, -phellandrene, and -myrcene were some of the most abundant volatiles in the analyzed oils. In silico analyses predicted 56 antifungal mechanisms, including inhibition of cell membrane and wall synthesis, affectation of primary metabolism, inhibition of molecular processes, redox homeostasis, and protein degradation and cutinase inhibition. The last one is a specific mechanism mediating in vivo plant-fungal interactions found exclusively in -terpinene and -ocimene. : Compounds with cutinase inhibition activity such as -terpinene and -ocimene are of great potential to complement the activity of other bioactive compounds. According to literature and in silico analyses the mixture of cinnamaldehyde, eugenol, -terpinene and -ocimene could be a potential formulation for the management of postharvest fungi.
Back to the Future: Repurposing Metformin, a Metabolically Active Drug, to Treat Mild-to-Moderate Ulcerative Colitis.
Antonelli E, Dell'Era A, Maconi G … +1 more , Bassotti G
Metabolites · 2026 Mar · PMID 42042883 · Full text
The incidence of ulcerative colitis, an entity belonging to the inflammatory bowel diseases, is rising worldwide. Due to the unpredictable nature of its clinical flares and the need for chronic treatment, ulcerative coli...
The incidence of ulcerative colitis, an entity belonging to the inflammatory bowel diseases, is rising worldwide. Due to the unpredictable nature of its clinical flares and the need for chronic treatment, ulcerative colitis has a huge burden of psychological impairment and reduced quality of life. Although several treatments are available to manage patients with ulcerative colitis, their efficacy is unpredictable, and long-term remission is often difficult to achieve. Moreover, the more recent and expensive drugs are not easily available in many countries. These facts have prompted the research in this field to focus on finding additional treatments for such patients. Among the putative repurposing drugs, metformin, an oral antidiabetic agent used for over seventy years, seems to represent a good candidate. While randomized controlled trials suggest that metformin, as an adjunct to conventional treatments, may improve clinical outcomes in mild-to-moderate ulcerative colitis, population-based observational and genetic studies offer mixed signals regarding its role in long-term disease modification or primary prevention. This, together with the wide availability and the low cost of metformin, might represent a good example of repurposing, as detailed in the present review. However, human mechanistic validation remains limited, underscoring the need for further research.
Serum Untargeted Metabolomics Integrated with SHAP-Based Machine Learning for Multiclass Stratification of Prostate Cancer, Prostatitis, and Benign Prostatic Hyperplasia.
Wang Z, Xin J, He Q … +4 more , Xu S, Wu J, Yang F, Dong L
Metabolites · 2026 Mar · PMID 42042882 · Full text
BACKGROUND: Prostate cancer, benign prostatic hyperplasia, and prostatitis share substantial overlap in clinical symptoms and biological characteristics, which hampers non-invasive and early differential diagnosis. Untar...
BACKGROUND: Prostate cancer, benign prostatic hyperplasia, and prostatitis share substantial overlap in clinical symptoms and biological characteristics, which hampers non-invasive and early differential diagnosis. Untargeted metabolomics enables comprehensive profiling of disease-associated metabolic alterations; however, its high dimensionality and strong feature correlations challenge conventional statistical approaches. METHODS: To address this, we analyzed serum untargeted LC-MS data following standardized preprocessing. We adopted a nested cross-validation strategy to evaluate various feature selection methods and machine learning classifiers, ultimately determining that multiclass LASSO regression was the most effective feature selection approach. RESULTS: An optimized Random Forest model demonstrated strong, superior performance in distinguishing between prostate cancer, prostatitis, benign prostatic hyperplasia, and healthy controls (out-of-fold accuracy: 93.8%; macro-F1: 0.937). Additionally, SHAP (SHapley Additive exPlanations) analysis translated feature statistical importance into biologically meaningful modules, revealing that distinct, disease-specific patterns of metabolic reprogramming drove the model's robust multiclass discrimination. CONCLUSIONS: This study demonstrates the value of integrating serum untargeted metabolomics with advanced explainable machine learning for effective multiclass differentiation of major prostate diseases, providing a promising non-invasive framework for diagnostic stratification and metabolic biomarker discovery.
EHMN 2026: A Thermodynamically Refined, SBML-Standardised Human Metabolic Network for Genome-Scale Analysis and QSP Integration.
Goryanin I, Slovianov L, Checkley S … +1 more , Goryanin I
Metabolites · 2026 Mar · PMID 42042881 · Full text
BACKGROUND: Genome-scale metabolic models (GEMs) are foundational tools for systems biology, enabling quantitative interrogation of human metabolism across physiological and pathological states. However, many legacy reco...
BACKGROUND: Genome-scale metabolic models (GEMs) are foundational tools for systems biology, enabling quantitative interrogation of human metabolism across physiological and pathological states. However, many legacy reconstructions exhibit heterogeneous identifier usage, incomplete pathway integration, and limited thermodynamic refinement, constraining reproducibility, interoperability, and translational applicability. METHODS: We present EHMN 2026, an update of the Edinburgh Human Metabolic Network. The reconstruction was refined through systematic identifier reconciliation using MetaNetX and ChEBI mappings, duplicate reaction consolidation, thermodynamic directionality assessment, and structured pathway annotation via Reactome. The final model was encoded in Systems Biology Markup Language (SBML) Level 3 Version 2 with the Flux Balance Constraints (FBC2) package, ensuring explicit gene-protein-reaction (GPR) representation and compatibility with modern constraint-based modelling toolchains. RESULTS: EHMN 2026 comprises 11 compartments, 14,321 metabolites (species), and 22,642 reactions, supported by 3996 gene products. Of all reactions, 9638 (42.6%) contain GPR associations, linking metabolic transformations to 2887 unique Ensembl gene identifiers (ENSG). Pathway integration yielded 2194 unique Reactome identifiers, providing structured pathway-level organisation of metabolic functions. Thermodynamic refinement reduced infeasible energy-generating cycles and improved reaction directionality coherence while preserving global network connectivity. The reconstruction is fully SBML-compliant and portable across major modelling platforms. Compared with Recon3D and Human1, EHMN 2026 uniquely combines native Reactome reaction-level annotation, systematic MetaNetX identifier harmonisation, documented thermodynamic cycle elimination (37 cycles, 0 remaining), and an 11-compartment architecture supporting organelle-specific modelling-features designed for QSP and multi-layer integration applications. CONCLUSIONS: EHMN 2026 delivers a rigorously harmonised, thermodynamically refined, and pathway-annotated human metabolic reconstruction with enhanced annotation depth and standards-based interoperability. By combining genome-scale coverage with structured gene and pathway integration, the model establishes a robust computational backbone for reproducible metabolic analysis and provides a scalable foundation for future multi-layer systems pharmacology and integrative modelling frameworks.
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