Metabolites最新文献

{"title":"Volatile Profiling and Transcriptomic Analysis of Peel and Flesh in Wampee (<i>Clausena lansium</i> (Lour.) Skeels).","authors":"Ruibing Xu, Qingshan Li, Gengrui Zhu, Yi Chen, Gaoyang Zhang","doi":"10.3390/metabo16080598","DOIUrl":"10.3390/metabo16080598","url":null,"abstract":"<p><p><b>Background</b>: Wampee (<i>Clausena lansium</i> (Lour.) Skeels) is an understudied Rutaceae crop native to southern China, whose fruit features a complex aroma profile with simultaneous sour, sweet, bitter and astringent notes. Although bioactive compounds including flavonoids, alkaloids and volatile oils in wampee fruit have been partially characterized, the tissue-specific metabolic and transcriptional basis underlying its distinctive aroma formation remains largely unclear. <b>Methods</b>: We performed an integrated volatile metabolomic and transcriptomic analysis on the pericarp (peel) and flesh of wampee fruit across three cultivars (Shanyellowpi, Heijingang, Bingtangxin). Volatile metabolites were profiled via headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS), and transcriptome profiles were generated by RNA-Seq. Multi-omics integration was conducted using Procrustes analysis, gene-metabolite correlation network construction and weighted gene co-expression network analysis (WGCNA). <b>Results</b>: A total of 288 volatile metabolites were identified, representing the most comprehensive volatile inventory for <i>C. lansium</i> reported to date. Principal component analysis and partial least squares discriminant analysis revealed distinct volatile profiles between pericarp and flesh; terpenoids were the dominant chemical class, accounting for 71.56-91.48% of total volatiles in pericarp and 61.88-67.22% in flesh. Notably, organoheterocyclic compounds were significantly enriched in Shanyellowpi flesh (40.45%), forming a cultivar-specific metabolic signature absent in the other two cultivars. Transcriptomic analysis showed that phenylpropanoid biosynthesis was the most significantly enriched pathway among differentially expressed genes, followed by monoterpene biosynthesis and sesquiterpenoid biosynthesis. Procrustes analysis demonstrated a strong global concordance between the two omics layers (M² = 0.535, <i>p</i> < 0.001). Gene-metabolite correlation networks identified terpene synthase (<i>TPS</i>) genes (<i>HP075360</i>, <i>HP217350</i>) and oxidoreductase genes (<i>SOD1</i>, <i>GST</i>, <i>10HGO</i>) as candidate co-regulators of terpenoid biosynthesis. WGCNA further prioritized <i>TPS</i> genes, cytochrome P450 genes and MYB transcription factor genes as key regulators driving volatile metabolic divergence between tissues. <b>Conclusion</b>: This study provides a comprehensive volatile and transcriptomic atlas of wampee fruit, and identifies tissue-specific and cultivar-specific metabolic signatures as well as their candidate regulatory genes. These findings advance our understanding of quality differentiation in Rutaceae fruits and lay a foundation for molecular breeding and flavor improvement of wampee.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13515103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Performance of Serum Xenopsin-Related Peptide-1 in Gestational Diabetes Mellitus: A Prospective Observational Study.","authors":"Yasin Karadag, Ozgur Ozdemır, Gulseren İpek Karadag, Erinç Tekin","doi":"10.3390/metabo16080595","DOIUrl":"10.3390/metabo16080595","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders during pregnancy and is associated with adverse maternal and neonatal outcomes. Xenopsin-Related Peptide-1 (XRP-1) has recently emerged as a potential regulator of glucose metabolism and insulin homeostasis. This study evaluated serum XRP-1 levels and assessed their diagnostic performance in women with GDM. <b>Methods</b>: In this prospective observational study, 120 pregnant women between 24 and 28 weeks of gestation were enrolled, including 60 women with GDM and 60 healthy controls. Serum XRP-1 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Clinical, biochemical, and obstetric characteristics were compared between groups. Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression were performed to evaluate the diagnostic performance and independent association of XRP-1 with GDM. <b>Results:</b> Serum XRP-1 levels were significantly higher in women with GDM than in healthy controls (3.45 ± 0.47 vs. 2.87 ± 0.46 ng/mL, <i>p</i> = 0.003). ROC analysis demonstrated moderate discriminatory performance for XRP-1 in identifying GDM (AUC = 0.658, 95% CI: 0.560-0.750), with an optimal cut-off value of 3.12 ng/mL, corresponding to 63.3% sensitivity and 61.7% specificity. Multivariable logistic regression demonstrated that serum XRP-1 remained independently associated with GDM after adjustment for maternal age, pre-pregnancy body mass index, gestational weight gain, and parity (adjusted OR 2.74, 95% CI 1.31-5.73; <i>p</i> = 0.007). HbA1c and C-reactive protein levels were also significantly higher in the GDM group. <b>Conclusions</b>: Serum XRP-1 concentrations were independently associated with GDM and demonstrated moderate diagnostic accuracy. Although XRP-1 cannot replace established diagnostic methods, it may represent a complementary biomarker for identifying gestational dysglycemia. Larger multicenter studies are required to validate its clinical utility.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13515266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinamide Mononucleotide Adenylyltransferase 1 and NAD⁺ Homeostasis in Neuroprotection and Aging.","authors":"You Sun, Bowei Li, Zhengjiang Qian","doi":"10.3390/metabo16080597","DOIUrl":"10.3390/metabo16080597","url":null,"abstract":"<p><p>Nicotinamide adenine dinucleotide (NAD⁺) is a fundamental metabolic cofactor and signaling molecule that supports redox reactions, DNA repair, chromatin regulation, stress adaptation, inflammation, and neuronal maintenance. Age-associated NAD⁺ decline has been implicated in brain aging and neurodegenerative disorders, but the causal node and limiting compartment differ across tissues and disease states. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1) catalyzes the final step in NAD⁺ biosynthesis and represents the major nuclear isoform of the mammalian NMNAT family. Direct human genetic evidence establishes NMNAT-1 as a causal gene in inherited retinal degeneration, whereas evidence linking endogenous NMNAT-1 to broader brain aging or sporadic neurodegeneration is mainly convergent preclinical, preliminary, or indirect. Beyond NAD⁺ synthesis, biochemical and Drosophila studies suggest possible chaperone-like and proteostasis-supporting functions, but a separable NAD⁺-independent function of endogenous mammalian NMNAT-1 has not yet been established in vivo. Here, we review the molecular structure, localization, and regulation of NMNAT-1, emphasizing calibrated distinctions among catalytic nuclear NAD⁺ supply, engineered axonal protection, pathway-adjacent NAD⁺ interventions, and putative non-catalytic protection. We further discuss how NMNAT-1 dysfunction may contribute to aging-associated genomic instability, neuroinflammation, synaptic impairment, retinal degeneration, selected neurodegenerative models, and glioma biology. Finally, we evaluate therapeutic strategies targeting NMNAT-1 and NAD⁺ pathways, noting that no human trial has yet established efficacy for an NMNAT-1-directed neurological therapy. A compartment-aware and evidence-stratified view is therefore essential for translating NMNAT-1 biology into interventions for age-related neural disease.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13515651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ciliary Neurotrophic Factor in Skeletal Muscle of Older Adults and the Effects of Weight Loss and Aerobic Training.","authors":"Alice S Ryan, Guoyan Li, Colleen Lynch, Sausan M Jaber, Galya Bigman","doi":"10.3390/metabo16080596","DOIUrl":"10.3390/metabo16080596","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Ciliary neurotrophic factor (CNTF), a pleiotropic cytokine with central and peripheral actions, has been implicated in obesity, insulin resistance, and aging, yet its role in skeletal muscle and cardiometabolic health remains unclear. This study examined skeletal muscle CNTF mRNA expression in relation to adiposity and glucose tolerance in older adults and assessed the effects of six-month weight loss (WL) and aerobic exercise training (AEX) interventions on its expression. <b>Methods:</b> Sixty-seven adults (age, 60.75 ± 7.58) underwent a vastus lateralis muscle biopsy, VO₂max testing, dual-energy X-ray absorptiometry (DXA) scan, a resting metabolic rate (RMR) and substrate oxidation assessment, and a 3-h oral glucose tolerance test with glucose and insulin area under the curve (AUC) calculation. A subset completed 6 months of either a WL program (<i>n</i> = 21) or a supervised 3 times per week AEX intervention (<i>n</i> = 20). <b>Results:</b> At baseline, skeletal muscle CNTF expression was inversely associated with RMR, fat oxidation, 3-h glucose AUC, and insulin AUC, but not with BMI, percent body fat, or VO₂max. WL reduced body weight, fat mass, glucose AUC, insulin AUC, and basal muscle CNTF expression, whereas AEX increased VO₂max and reduced fat mass without altering body weight, glucose AUC, insulin AUC, or basal CNTF. Insulin-stimulated CNTF expression increased after both WL and AEX, and the intervention-induced change in glucose disposal (M) was positively associated with the change in insulin-stimulated CNTF. <b>Conclusions:</b> In older adults, skeletal muscle CNTF is associated with glucose intolerance but is not associated with body composition or aerobic fitness. Improvements in insulin sensitivity are associated with increases in muscle CNTF during hyperinsulinemia. Further work is needed to determine the mechanism for muscle CNTF change during hyperinsulinemia after weight loss and exercise training, and its role in glucose metabolism and obesity in older adults.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13515990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning-Integrated Metabolomics for Precision Pharmacotherapy: Advances, Challenges, and Clinical Translation.","authors":"Pan Li, Jing Mao, Xianglin Hu, Yujiao Hu, Xiaoke Zhang, Qian Zheng, Xiaoying Hou, Yuchen Liu, Min Huang","doi":"10.3390/metabo16080600","DOIUrl":"10.3390/metabo16080600","url":null,"abstract":"<p><p>Machine learning (ML) integrated with metabolomics has emerged as a promising strategy to advance precision pharmacotherapy, enabling data-driven prediction of drug response. This review provides an overview of commonly applied ML methodologies in metabolomics-based pharmacological studies, including supervised models (Random Forest, Extreme Gradient Boosting, Support Vector Machine, Logistic Regression, K-Nearest Neighbors), unsupervised models (K-Means Clustering, Principal Component Analysis), and deep learning approaches. We summarize recent progress in the application of metabolomics-driven ML to personalized medication, with a focus on drug dosage optimization, therapeutic efficacy prediction, and adverse drug reaction assessment. Despite these advances, significant challenges remain, including limited explainability, insufficient prospective clinical validation, lack of standardization and reproducibility, and data dimensionality and quality issues. Addressing these issues will be essential for the clinical translation of ML-metabolomics integration. Looking ahead, continued methodological innovation, large-scale multi-center prospective validation, and integration with other omics platforms will be key to unlocking the full potential of metabolomics combined with ML in precision healthcare.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13515566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mammalian Arachidonic Acid 15-Lipoxygenases: Fed-Batch Fermentation, Enzyme Purification and Functional Characterization.","authors":"Vladislav Aksenov, Angelina V Kurchatova, Alexey Golovanov, Veronika Ulasenko, Olga Zubkova, Alexander Zhuravlev, Ekaterina Makishvili, Nikolay E Kushlinskii, Hartmut Kuhn, Igor Ivanov","doi":"10.3390/metabo16080599","DOIUrl":"10.3390/metabo16080599","url":null,"abstract":"<p><strong>Background: </strong>Mammalian arachidonic acid lipoxygenases (ALOXs) are non-heme iron-containing enzymes that oxygenate polyunsaturated fatty acids (PUFAs) with at least two isolated double bonds to hydroperoxy derivatives. The patho-physiological roles of these enzymes in inflammatory, hyperproliferative, and neurological diseases have made them promising targets for pharmacological interventions. Unfortunately, the expression levels of ALOX isoforms in mammalian cells are very low, which makes functional characterization of native enzymes and the development of isoform-specific inhibitors challenging.</p><p><strong>Methods: </strong>Here, we developed a unifying experimental protocol for fed-batch fermentation of mammalian ALOX isoforms in a bioreactor, followed by purification of the recombinant proteins and their functional characterization.</p><p><strong>Results: </strong>Our methodological protocol allowed the preparation of mg amounts of catalytically active human ALOX15, mouse Alox15 and human ALOX15B. The purified proteins are suitable for high-throughput inhibitor screening assays but can also be used as antigens for the preparation of isoform-specific antibodies and for direct structural analyses. Antibodies cross-reacting with human ALOX15 and ALOX15B have been detected in the blood of patients suffering from colorectal cancer.</p><p><strong>Conclusions: </strong>Our functional ALOX data stresses the catalytic differences between mouse and human ALOX15 orthologs, and these catalytic peculiarities need to be considered when the results of mechanistic studies obtained in mouse models of human diseases are transferred to the human situation.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13515856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Effects of Combined Resistance Exercise and Vitamin D Supplementation on Cardiometabolic Profiles and Functional Capacities in Elderly Women with Type 2 Diabetes.","authors":"Hyoung-Jun Kim, Deok-Su Yoo, Man-Gyoon Lee","doi":"10.3390/metabo16080593","DOIUrl":"10.3390/metabo16080593","url":null,"abstract":"<p><p><b>Background/Objectives</b>: This 12-week randomized controlled trial investigated whether progressive resistance training combined with vitamin D supplementation produces enhanced combined improvements in cardiometabolic profiles and functional capacities compared with monotherapies in elderly Korean women with type 2 diabetes mellitus (T2DM) and vitamin D deficiency. <b>Methods</b>: In a 2 × 2 factorial design, 52 women (aged 65-80 years) with T2DM and serum 25(OH)D < 20 ng/mL were assigned to four groups: Exercise + Vitamin D (Ex + VitD, <i>n</i> = 15), Exercise + Placebo (Ex + Placebo, <i>n</i> = 13), Vitamin D only (VitD, <i>n</i> = 11), or Control (<i>n</i> = 13). Exercise groups completed supervised progressive resistance training three times weekly, and vitamin D groups received 2000 IU/day cholecalciferol. <b>Results</b>: The Ex + VitD group achieved significant improvements in HbA1c (-0.13%, <i>p</i> = 0.019), fasting glucose (-0.79 mmol/L, <i>p</i> < 0.001), insulin (-1.96 μU/mL, <i>p</i> = 0.050), and HOMA-IR (-0.77, <i>p</i> = 0.020). Serum 25(OH)D increased substantially (+15.57 ng/mL, <i>p</i> < 0.001). Calcitonin rose exclusively in the Ex + VitD group (+2.57 pg/mL, <i>p</i> < 0.001, d = 3.34), while monotherapies showed no change. Total cholesterol (-23.93 mg/dL), triglycerides (-25.07 mg/dL), and LDL-cholesterol (-10.20 mg/dL) decreased significantly. Both exercise groups showed marked strength gains (chair stand +8.33 to +10.00 repetitions, <i>p</i> < 0.001) and balance improvements (functional reach +2.47 to +4.46 cm, <i>p</i> ≤ 0.033). <b>Conclusions</b>: Twelve weeks of progressive resistance training combined with vitamin D supplementation produced enhanced combined improvements in glycemic control, insulin sensitivity, calcitonin secretion, muscular strength, and lipid metabolism in elderly women with T2DM and vitamin D deficiency, targeting complementary pathways that neither intervention engaged alone.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13515638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDCA Supplementation During Maternal High-Fat Diet Exposure Is Associated with Offspring Gut Microbiota at Weaning and Adult Metabolic Phenotypes in a Mouse Model.","authors":"Halizere Simayi, Yating Yang, Li Gao, Bin Yu, Yuwen Shi, Ningxin Chen, Jialing He, Meng Duan, Wei He, Shankuan Zhu, Fei Yang","doi":"10.3390/metabo16080590","DOIUrl":"10.3390/metabo16080590","url":null,"abstract":"<p><p><b>Background/Objective</b>: Maternal diet is an important determinant of gut microbiota composition in dams and offspring. This study investigated whether HDCA supplementation during maternal high-fat diet (HFD) exposure was associated with gut microbiota composition in dams and offspring and with selected obesity-related phenotypes. <b>Methods</b>: Nineteen C57BL/6J female mice were assigned to a control diet group (CON), a high-fat diet group (HFD), and a high-fat diet supplemented with 0.5% hyodeoxycholic acid group (HFD+HDCA). Fecal samples were collected from the dams before mating, following 8 weeks of dietary intervention, and from the offspring at weaning. All samples were analyzed using 5R 16S rRNA gene sequencing. Body weight was monitored in both dams and offspring, and liver histology was assessed by hematoxylin and eosin staining. <b>Results</b>: HFD exposure was associated with obesity-related phenotypes in dams and offspring, including increased maternal body weight and greater hepatic lipid accumulation and visceral adiposity in offspring. LEfSe and ANCOM-BC2 analyses identified concordant microbial changes between dams and offspring under corresponding dietary conditions. <i>Lachnospiraceae_Unknown_genus3261</i> and <i>Coprococcus</i> increased with HFD exposure in both dams and offspring, whereas <i>Bifidobacterium</i>, <i>Coprococcus</i>, and <i>Allobaculum</i> decreased following HDCA supplementation. These findings indicate maternal-offspring concordance in microbiota responses to HFD and HDCA, without establishing direct vertical transmission. PICRUSt2 analysis suggested group association differences in predicted functional potential for pathways annotated to propionate, pyruvate, and β-alanine metabolism. <b>Conclusions</b>: HDCA supplementation during maternal HFD exposure was associated with differences in offspring gut microbiota at weaning and with attenuation of selected obesity-related phenotypes. These findings suggest a potential role of the gut microbiota-bile acid axis in mediating intergenerational dietary effects. However, the study does not establish direct microbial transmission, altered metabolic activity, or causality; these findings require confirmation in litter-aware and mechanistic studies.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13515643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Dietary <i>Peganum harmala</i> Stem Ethanolic Extract on Serum Inflammatory and Antioxidant Markers, Duodenal Metabolomic Features, and Hepatic Transcriptomic Profiles in Hu Sheep.","authors":"Bo Wang, Cunxi Nie, Yanfeng Liu, Rongyan Qin, Wenqi Wang, Yanfen Cheng","doi":"10.3390/metabo16080591","DOIUrl":"10.3390/metabo16080591","url":null,"abstract":"<p><p><b>Background:</b><i>Peganum harmala</i> L. stem ethanolic extract (PHL) has been scarcely evaluated as a ruminant feed component. We evaluated its effects on serum inflammatory and antioxidant biomarkers and duodenal and hepatic molecular responses in Hu sheep. <b>Methods:</b> Twelve male Hu sheep, approximately 120 days old, were randomly assigned to a control group or a PHL treatment group (<i>n</i> = 6 per group). After a 7-day adaptation period, the PHL group received 3 g/head/day of PHL (total flavonoid content: 65.7 mg rutin equivalents (RE)/g; approximately 197.1 mg RE/head/day) for 50 days. Serum markers, duodenal untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics, liver RNA sequencing, and alternative splicing were analyzed. <b>Results:</b> Serum interleukin-6 and malondialdehyde were lower, whereas interleukin-4 and glutathione peroxidase were higher, in the PHL group than in the control group (<i>p</i> < 0.05). Using variable importance in projection ≥ 1, fold change ≥ 1.2 or ≤0.83, and unadjusted <i>p</i> < 0.05 as screening criteria, 479 LC-MS features met these nominal screening criteria, of which 81 had database annotations. Following Benjamini-Hochberg correction, only two features remained significant (q < 0.05); however, only one was successfully annotated, rendering the pathway analysis exploratory. Liver RNA sequencing identified 279 differentially expressed genes (absolute log₂FC ≥ 1 and q ≤ 0.001) and 104 skipped-exon events (false discovery rate < 0.05). Functional enrichment analysis highlighted annotations related to bile secretion, ATP-binding cassette transport, nutrient metabolism, and glutathione metabolism. <b>Conclusions:</b> PHL supplementation was associated with selective changes in serum inflammatory and antioxidant biomarkers, accompanied by hepatic molecular responses. The duodenal metabolomic findings remain exploratory, and dose-response studies incorporating alkaloid quantification and targeted molecular validation are required before practical application can be considered.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13515815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold-Induced Elevation of 3-Hydroxypropionate Exacerbates Colitis by Remodeling Gut Microbiota and Impairing Mitochondrial Respiration in Intestinal Epithelial Cells.","authors":"Yankun Jia, Baodong Gao, Kefei Wu, Mengjie Gao, Qi Lin, Tu Qian, Junjie Ma, Hongyu Zhang, Ping Zhu, Zhinan Chen, Yue Zhai","doi":"10.3390/metabo16080592","DOIUrl":"10.3390/metabo16080592","url":null,"abstract":"<p><strong>Background/objectives: </strong>Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder influenced by environmental factors including cold stress. While cold exposure exacerbates intestinal inflammation, the specific microbial metabolites linking environmental stress to colitis remain unclear. 3-Hydroxypropionate (3-HPA) is a gut microbial metabolite elevated following cold exposure, but its pathogenic role in intestinal inflammation has not been investigated. This study aimed to determine whether 3-HPA contributes to colitis progression and to characterize its effects on gut microbiota and intestinal epithelial function.</p><p><strong>Methods: </strong>We employed a dextran sulfate sodium (DSS)-induced colitis mouse model to assess the impact of cold exposure and exogenous 3-HPA administration. Paired shotgun metagenomic and metabolomic analyses were performed to evaluate gut microbial composition and metabolic outputs. Mechanistic studies using NCM460 intestinal epithelial cells were conducted to examine mitochondrial respiration and tight junction integrity under nutrient-limited conditions.</p><p><strong>Results: </strong>Cold exposure increased fecal 3-HPA levels and aggravated DSS-induced colitis, characterized by enhanced weight loss, histological damage, and immune cell infiltration. Direct 3-HPA supplementation alone was sufficient to worsen colitis severity. Multi-omics profiling revealed that 3-HPA reshaped gut microbiota composition, depleted short-chain fatty acids (SCFAs), and disrupted microbial tryptophan and bile acid metabolism. In vitro, 3-HPA impaired mitochondrial oxidative phosphorylation, reduced ATP production, and compromised tight junction organization in intestinal epithelial cells.</p><p><strong>Conclusions: </strong>These findings identify 3-HPA as a gut microbial metabolite elevated by cold exposure that contributes to colitis progression by disrupting beneficial microbial metabolism while also impairing epithelial mitochondrial function and barrier integrity. Modulating 3-HPA production or its downstream epithelial effects may represent a potential therapeutic approach for IBD exacerbated by environmental stress.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13515263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}