Metabolites最新文献

{"title":"Review: Piglets' (Re)Feeding Patterns, Mineral Metabolism, and Their Twisty Tail.","authors":"Theo van Kempen, Eugeni Roura","doi":"10.3390/metabo15070480","DOIUrl":"https://doi.org/10.3390/metabo15070480","url":null,"abstract":"<p><p>The appearance rate of nutrients into systemic circulation affects hormones like insulin and through that efficiency of growth. This also affects mineral requirements critical for metabolism, notably phosphate (P), magnesium (Mg), and potassium (K). Fasting animals have a downregulated metabolism, upon which P, Mg, and K are exported from their cells into the blood and are subsequently excreted in their urine. Abrupt resumption of feed intake, especially of highly glycemic feeds, creates an acute need for these minerals, which can result in deficiency symptoms, particularly with P deficiency. In human medicine, this is called refeeding syndrome: a large meal after a period of fasting can prove fatal. Young animals seem to be especially sensitive, likely driven by their ability to grow rapidly and thus to drastically upregulate their metabolism in response to insulin. Symptoms of P deficiency are fairly a-specific and, consequently, not often recognized. They include edema, which makes it appear as if piglets are growing well, explaining the high gain/feed rate typically seen immediately after weaning, even when piglets are eating at or below the maintenance requirements. Phosphate deficiency can also result in hypoxia and hypercarbia, which may trigger ear necrosis, <i>Streptococcus suis</i> infections, or even death. Hypophosphatemia can also trigger rhabdomyolysis, which may contribute to tail-biting, but this requires further study. Arguably, when fasting cannot be avoided, diets for newly weaned piglets should be formulated to avoid these problems by lowering their glycemic load and by formulating diets according to the piglets' actual requirements inspired by their genuine intake and health and not simply by extrapolating from older animals.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Mitochondrial Dynamics and Reactive Oxygen Species Levels with Reduced Antioxidant Defenses in Human Epicardial Adipose Tissue.","authors":"Ana Burgeiro, Diana Santos, Ana Catarina R G Fonseca, Inês Baldeiras, Ermelindo C Leal, João Moura, João Costa-Nunes, Patrícia Monteiro Seraphim, Aryane Oliveira, António Canotilho, Gonçalo Coutinho, David Prieto, Pedro Antunes, Manuel Antunes, Eugenia Carvalho","doi":"10.3390/metabo15070481","DOIUrl":"https://doi.org/10.3390/metabo15070481","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Epicardial adipose tissue (EAT) is metabolically active and is in dynamic crosstalk with the surrounding cardiomyocytes, modulating their function and metabolism. Oxidative stress is a key contributor to cell death and cardiac remodeling, is a hallmark of diabetes (DM) and cardiovascular disease, such as coronary artery disease (CAD). However, little is known about these processes in EAT from patients undergoing cardiac surgery. This study investigates changes in mitochondrial dynamics, reactive oxygen species (ROS) production, and antioxidant defense levels in EAT compared to subcutaneous adipose tissue (SAT) in patients undergoing cardiac surgery, with a focus on the impact of DM and CAD. <b>Methods</b>: Adipose tissue biopsies were collected from 128 patients undergoing surgical cardiac intervention. Mitochondrial dynamics and oxidative stress markers were analyzed. <b>Results</b>: EAT exhibited increased expression of mitochondrial fusion markers [mitofusin 1 (<i>p</i> ≤ 0.001), mitofusin 2 (<i>p</i> = 0.038), and optic atrophy 1 (<i>p</i> ≤ 0.001)], as well as fission markers [fission 1 <i>(p</i> ≤ 0.001) and dynamin-related protein 1 (<i>p</i> ≤ 0.001)] relative to SAT. Additionally, ROS levels (dihydroethidium, <i>p</i> = 0.004) were elevated, while lipid peroxidation (malondialdehyde, <i>p</i> ≤ 0.001) was reduced in EAT compared to SAT. Reduced glutathione (GSH) levels (<i>p</i> ≤ 0.001) and the redox buffer ratio between reduced and oxidized glutathione (GSH/GSSG, <i>p</i> ≤ 0.001) were significantly increased in EAT. Interestingly, glutathione peroxidase activity (<i>p</i> ≤ 0.001) and the antioxidant defense markers catalase (<i>p</i> ≤ 0.001) and superoxide dismutase 2 (<i>p</i> = 0.001) were significantly reduced in EAT compared to SAT. <b>Conclusions</b>: The findings provide a unique molecular insight into the mitochondrial dynamics and oxidative stress profiles of EAT, highlighting potential avenues for a novel diagnostic method and therapeutic strategies for cardiac disease.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Complexity of Oxidative Stress in Human Age-Related Diseases-A Review.","authors":"Alicja Płóciniczak, Ewelina Bukowska-Olech, Ewa Wysocka","doi":"10.3390/metabo15070479","DOIUrl":"https://doi.org/10.3390/metabo15070479","url":null,"abstract":"<p><p>The aging process is a complex and dynamic phenomenon influenced by genetic, environmental, and biochemical factors. One of the key contributors to aging and age-related diseases is oxidative stress, resulting from an imbalance between the generation of reactive oxygen species (ROS) and the efficiency of antioxidant defense systems. In this review, we introduce the concept of the oxidative stress complexity-a network encompassing ROS-generating systems, enzymatic and non-enzymatic antioxidants, and genetic determinants that collectively shape redox homeostasis. Emerging research highlights the significant influence of genetic variability on the activity and expression of selected and most examined antioxidant enzymes, including superoxide dismutase (SOD), paraoxonase 1 (PON1), catalase (CAT), and glutathione peroxidase (GPX), thereby modulating individual susceptibility to oxidative damage, disease onset, and the pace of aging. Particular attention is paid to the interplay among oxidative stress, chronic inflammation, and metabolic dysfunction in the pathogenesis of various age-related disorders. By integrating findings from molecular studies, clinical research, and population genetics, we discuss the diagnostic and prognostic potential of antioxidant enzymes as biomarkers of aging and explore strategies for redox-modulating interventions. Understanding these interrelations is essential for identifying biomarkers of biological aging and developing personalized strategies aimed at promoting healthy aging and reducing the risk of chronic disease.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Dietary Supplementation of Chestnut Tannic Acid on the Growth Performance, Gut Morphology and Microbiota of Weaned Piglets.","authors":"Jinzhou Zhang, Yuting Zhang, Yuya Wang, Yanwei Li, Dongyang Liu, Hongbing Xie, Yongqiang Wang, Meinan Chang, Liping Guo, Zhiguo Miao","doi":"10.3390/metabo15070477","DOIUrl":"https://doi.org/10.3390/metabo15070477","url":null,"abstract":"<p><p><b>Background/Objectives</b>: This study investigated the effects of chestnut tannic acid (TA) on the growth performance, the expression of tight junction proteins and the composition of the gut microbiota of weaned piglets, which could provide novel insights into the application of TA in swine production. <b>Methods</b>: In a 42-day trial, 180 healthy, 21-day-old Duroc × Landrace × Yorkshire piglets were randomly assigned to a Control group and four treatment groups (TA1-4), fed commercial diets supplemented with 0, 0.06%, 0.12%, 0.18% or 0.24% TA. Each group had six replicates of six pigs each. <b>Results</b>: The average daily gain in all TA groups, the jejunal and ileal villus height and the villus height-to-crypt depth ratio in the TA3 and TA4 groups were markedly increased (<i>p</i> < 0.05). The mRNA levels of <i>MUC2</i> and <i>ZO-1</i> were upregulated in the TA3 group, as were those of <i>MUC4</i> in the jejunum and ileum and <i>claudin</i> in the duodenum and ileum; glutathione peroxidase and total antioxidant capacity were upregulated in the duodenum and jejunum in the TA3 group, and total superoxide dismutase was increased in all the TA2 groups (<i>p</i> < 0.05). Conversely, the malondialdehyde significantly decreased in all the TA groups (<i>p</i> < 0.05). TA supplementation improved the alpha diversity of the intestinal microflora and augmented probiotic abundance while reducing that of pathogenic bacteria. The contents of acetic, isobutyric, valeric, isovaleric, hexanoic and propionic acids, as well as total short-chain fatty acids (SCFA), were higher in the TA2 and TA3 groups (<i>p</i> < 0.05). <b>Conclusions</b>: TA inclusion in piglet diets improved the intestinal environment by upregulating the antioxidant enzymes, improving intestinal morphology and promoting probiotic growth and SCFA production while reducing pathogenic bacterial abundance, consequently enhancing the gut barrier and the growth of weaned piglets.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Probiotics, Prebiotics, Synbiotics, and Postbiotics in Livestock and Poultry Gut Health: A Review.","authors":"Taojing Yue, Yanan Lu, Wenli Ding, Bowen Xu, Cai Zhang, Lei Li, Fuchun Jian, Shucheng Huang","doi":"10.3390/metabo15070478","DOIUrl":"https://doi.org/10.3390/metabo15070478","url":null,"abstract":"<p><strong>Background: </strong>The gut health of livestock and poultry is of utmost importance as it significantly impacts their growth performance, disease resistance, and product quality. With the increasing restrictions on antibiotic use in animal husbandry, probiotics, prebiotics, synbiotics, and postbiotics (PPSP) have emerged as promising alternatives. This review comprehensively summarizes the roles of PPSP in promoting gut health in livestock and poultry.</p><p><strong>Results: </strong>Probiotics, such as <i>Lactobacillus</i>, <i>Bifidobacterium</i>, and <i>Saccharomyces</i>, modulate the gut microbiota, enhance the gut barrier, and regulate the immune system. Prebiotics, including fructooligosaccharides, isomalto-oligosaccharides, galactooligosaccharides, and inulin, selectively stimulate the growth of beneficial bacteria and produce short-chain fatty acids, thereby improving gut health. Synbiotics, combinations of probiotics and prebiotics, have shown enhanced effects in improving gut microbiota and animal performance. Postbiotics, consisting of inanimate microorganisms and their constituents, restore the gut microbiota balance and have anti-inflammatory and antibacterial properties. Additionally, the review looks ahead to the future development of PPSP, emphasizing the importance of encapsulation technology and personalized strategies to maximize their efficacy.</p><p><strong>Conclusions: </strong>Our aim is to provide scientific insights for PPSP to improve the gut health of livestock and poultry.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-Sectional and Longitudinal Assessment of Sociodemographic and Lifestyle Determinants of Metabolic Syndrome and Hypertriglyceridemic Waist Phenotypes in 139,634 Spanish Workers.","authors":"Joan Obrador de Hevia, Ángel Arturo López-González, José Ignacio Ramírez-Manent, Carla Busquets-Cortés, Pedro Juan Tárraga López, Pere Riutord-Sbert","doi":"10.3390/metabo15070474","DOIUrl":"https://doi.org/10.3390/metabo15070474","url":null,"abstract":"<p><p><b>Objective:</b> The objective of this study was to analyze the prevalence and key sociodemographic and lifestyle determinants of metabolic syndrome (MetS) and the hypertriglyceridemic waist (HTGW) phenotype in a large occupational cohort. <b>Background:</b> Metabolic syndrome (MetS) and the hypertriglyceridemic waist (HTGW) phenotype, defined as the simultaneous presence of elevated waist circumference and high triglyceride levels, are major predictors of cardiometabolic morbidity and mortality. Despite their clinical relevance, data on their distribution and determinants in large occupational populations remain limited. <b>Methods:</b> A cross-sectional analysis was conducted on 139,634 employed adults (56,352 women and 83,282 men) across Spain, based on standardized clinical evaluations and validated questionnaires assessing physical activity, diet, smoking, alcohol consumption, education, and occupational class. Logistic regression models were used to estimate associations with MetS and HTGW. A longitudinal subsample of 40,431 individuals was followed over a 10-year period (2009-2019) to assess trends in metabolic risk phenotypes. <b>Results:</b> Male sex, older age, lower educational attainment, and unhealthy lifestyle behaviors were associated with a higher prevalence of both MetS and the HTGW phenotype. Physical inactivity, low adherence to the Mediterranean diet, and alcohol consumption were significantly associated with increased risk. The HTGW phenotype proved useful in identifying high-risk individuals, with a steadily increasing prevalence over time. <b>Conclusions:</b> Sociodemographic disparities and modifiable lifestyle factors significantly influence the prevalence and progression of MetS and HTGW in the Spanish workforce. Preventive strategies should emphasize early workplace screening, promotion of healthy behaviors, and reduction in educational and socioeconomic inequalities to mitigate cardiometabolic risk.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EM Dipeptide Enhances Milk Protein Secretion: Evidence from Integrated Metabolomic and Transcriptomic Analysis.","authors":"Yuqing Liu, Yuhao Yan, Runjun Yang, Xiaohui Li, Chuang Zhai, Xuan Wu, Xibi Fang, Boqun Liu","doi":"10.3390/metabo15070476","DOIUrl":"https://doi.org/10.3390/metabo15070476","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Breast milk provides essential nutrition and immune protection to support infant growth and development. However, insufficient breast milk remains a serious issue, and bioactive peptides represent a potential strategy to promote lactation. In this study, we investigated the impact of a methionine-containing dipeptide, EM, on MCF-10A mammary epithelial cells. <b>Methods:</b> MCF-10A cells were treated with EM, and cell proliferation and the expression of key milk protein genes were assessed. Integrated transcriptomic and untargeted metabolomic analyses were performed to identify EM-induced changes in metabolic and gene expression pathways. <b>Results:</b> EM treatment significantly enhanced cell proliferation and upregulated the expression of key milk protein genes (CSN1S1 (casein alpha-S1, encoding alpha-S1 casein), CSN2 (casein beta, encoding beta-casein), and CSN3 (casein kappa, encoding kappa-casein)) at both transcriptional and protein levels compared to controls. Integrated transcriptomic and metabolomic analyses revealed that EM reprogrammed amino acid metabolism, lipid biosynthesis, and nutrient transport pathways. Core genes such as SLC7A11, APOE, and ABCA1 were identified as critical nodes linking metabolic and transcriptional networks. <b>Conclusions:</b> These findings indicate that EM may promote lactogenic activity by modulating metabolic and transcriptional networks <i>in vitro</i>, highlighting the potential of dipeptide-based nutritional interventions, which warrants further <i>in vivo</i> validation.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary Study to Understand the Role of Gut Microbiota in Coronary Slow Flow Phenomenon (CSFP).","authors":"Tayfun Gurol, Tayyip Karaman, Yesim Gurol, Osman Ugur Sezerman, Sinem Oktem Okullu","doi":"10.3390/metabo15070475","DOIUrl":"https://doi.org/10.3390/metabo15070475","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Coronary slow flow phenomenon (CSFP) is a cardiovascular condition characterized by delayed passage of contrast medium through the coronary arteries, predominantly affecting young male smokers admitted with acute coronary syndrome. Although over 80% of patients experience recurrent chest pain and more than 20% require readmission, the etiology of CSFP remains poorly understood. Given the emerging role of gut microbiome in cardiovascular diseases, this study investigates the microbial composition associated with CSFP. <b>Methods:</b> Stool samples were collected from patients diagnosed with CSFP and healthy control individuals. Microbiota profiling was performed using 16S rRNA sequencing. Taxonomic differences were evaluated to identify microbial markers potentially associated with CSFP. <b>Results:</b> The analysis revealed a notable enrichment of the genus <i>Gemmiger</i> and the species <i>Anaerobutyricum</i> in CSFP patients, specifically within the selenium metabolism pathway. This is of particular interest given the established link between selenium deficiency and heightened cardiovascular risk, suggesting a possible microbiome-mediated modulation of selenium bioavailability in CSFP pathophysiology. Moreover, a marked increase in taxa associated with the biosynthesis of trimethylamine (TMA), a proatherogenic metabolite implicated in the onset and progression of various cardiovascular disorders, was observed in the CSFP cohort, further supporting a potential mechanistic role of gut microbiota in the disease's underlying etiology. <b>Conclusions:</b> Although statistical significance could not be established due to the limited sample size, the observed trends support the hypothesis that specific gut microbes and metabolic pathways, particularly those linked to selenium metabolism and TMA production, may serve as potential microbial indicators for CSFP. These preliminary findings warrant further investigation in larger cohorts.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerobic Exercise Delays Age-Related Sarcopenia in Mice via Alleviating Imbalance in Mitochondrial Quality Control.","authors":"Danlin Zhu, Lian Wang, Haoyang Gao, Ze Wang, Ke Li, Xiaotong Ma, Linlin Zhao, Weihua Xiao","doi":"10.3390/metabo15070472","DOIUrl":"https://doi.org/10.3390/metabo15070472","url":null,"abstract":"<p><p><b>Background:</b> Sarcopenia is a syndrome associated with aging, characterized by a progressive decline in skeletal muscle mass and function. Its onset compromises the health and longevity of older adults by increasing susceptibility to falls, fractures, and various comorbid conditions, thereby diminishing quality of life and capacity for independent living. Accumulating evidence indicates that moderate-intensity aerobic exercise is an effective strategy for promoting overall health in older adults and exerts a beneficial effect that mitigates age-related sarcopenia. However, the underlying molecular mechanisms through which exercise confers these protective effects remain incompletely understood. <b>Methods:</b> In this study, we established a naturally aging mouse model to investigate the effects of a 16-week treadmill-based aerobic exercise regimen on skeletal muscle physiology. <b>Results:</b> Results showed that aerobic exercise mitigated age-related declines in muscle mass and function, enhanced markers associated with protein synthesis, reduced oxidative stress, and modulated the expression of genes and proteins implicated in mitochondrial quality control. Notably, a single session of aerobic exercise acutely elevated circulating levels of β-hydroxybutyrate (β-HB) and upregulated the expression of BDH1, HCAR2, and PPARG in the skeletal muscle, suggesting a possible role of β-HB-related signaling in exercise-induced muscle adaptations. However, although these findings support the beneficial effects of aerobic exercise on skeletal muscle aging, further investigation is warranted to elucidate the causal relationships and to characterize the chronic signaling mechanisms involved. <b>Conclusions:</b> This study offers preliminary insights into how aerobic exercise may modulate mitochondrial quality control and β-HB-associated signaling pathways during aging.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacometabolomics Study of Sulfamethoxazole and Trimethoprim in Kidney Transplant Recipients: Real-World Metabolism and Urinary Excretion.","authors":"Marieke A J Hof, Hessel de Haan, Stepan Stepanovic, Stephan J L Bakker, Eelko Hak, Gérard Hopfgartner, Frank Klont, TransplantLines Investigators","doi":"10.3390/metabo15070473","DOIUrl":"https://doi.org/10.3390/metabo15070473","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The increased use of antibiotics is raising concerns about environmental contamination and antibiotic resistance, exemplified by the case of cotrimoxazole, a widely prescribed combination of sulfamethoxazole and trimethoprim. After oral administration and absorption, both drugs are excreted in their parent and metabolized forms, which is a factor that is commonly considered in environmental studies. Many studies, however, rely on pharmacokinetic data from drug developers, who mostly investigate drug metabolism in healthy male volunteers rather than in actual patient populations. <b>Methods</b>: We investigated the real-world metabolism and urinary excretion of cotrimoxazole in an LC-SWATH/MS-based pharmacometabolomics study of 149 kidney transplant recipients who took part in the TransplantLines Biobank and Cohort Study (NCT0327284). <b>Results</b>: Our study confirmed (as \"putatively characterized compound classes\") the presence of all the expected metabolites, and we (putatively) identified several previously unreported metabolites, including glucuronide conjugates of both drugs and two isoxazole ring-opened variants of sulfamethoxazole. The relative metabolite profiles furthermore indicated that the active drug trimethoprim accounted for 75% of the total signal intensity. For sulfamethoxazole, its acetylated metabolite was the main metabolite (59%), followed by the active parent drug (17%) and its glucuronide (7%). Alongside trimethoprim, these substances could serve as analytical targets for environmental cotrimoxazole monitoring, given their abundance (all three substances), activity (parent drug), and/or back-transformation potential (both conjugated metabolites). The isoxazole ring-opened variants (2-3%) may also warrant attention, considering their (presumed) absolute excreted quantities and potential pharmacological activity. <b>Conclusions</b>: This study underscores the value of pharmacometabolomics in elucidating real-world metabolite profiles, and it provides novel insights into cotrimoxazole metabolism and excretion, with implications for environmental and clinical monitoring.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}