Metabolomics最新文献

{"title":"Search for new biomarkers using metabolomic analysis reflective of intestinal permeability in healthy Japanese participants.","authors":"Masashi Morifuji, Miyabi Yasuda, Saori Takahashi, Asako Sato","doi":"10.1007/s11306-025-02270-y","DOIUrl":"https://doi.org/10.1007/s11306-025-02270-y","url":null,"abstract":"<p><strong>Introduction: </strong>Improving intestinal barrier function may prevent the development of a variety of diseases. The lactulose-to-mannitol ratio (L/M) is the most widely used intestinal permeability test, but it lacks convenience and practicality.</p><p><strong>Objectives: </strong>This study aims to validate the analysis of the relationship between L/M and metabolites in biological samples from two study populations, and to identify novel biomarkers that could increase sensitivity or simplify the detection of intestinal permeability.</p><p><strong>Methods: </strong>After screening 115 people for this study, plasma, urine, and fecal samples were collected from eligible participants and L/M tests were conducted. Metabolomic analysis of samples was performed using HPLC-MS/MS.</p><p><strong>Results: </strong>Data from 108 participants with available L/M test data were used for the analysis population. Participants were stratified into quartiles according to upper (positive) and lower (negative) quartile L/M test values. Candidate biomarkers of intestinal permeability was selected using comparison between two groups, partial least squares discriminant analysis (PLS-DA) and receiver operating characteristic (ROC) curves. Metabolites from plasma (n = 12), urine (n = 15), and feces (n = 36) were identified as candidate biomarkers of intestinal permeability. Data from another study comprising 149 participants was similarly analyzed, using the data from another study as the validation population. Several metabolites in plasma (n = 2), urine (n = 3), and feces (n = 3) were commonly detected in the analysis and validation populations. In feces, the predicted value using two metabolites resulted in an area under the curve of 0.853, surpassing that for a single metabolite.</p><p><strong>Conclusions: </strong>Single or combined biological metabolites represented potential biomarkers for determining intestinal permeability. Evaluation of intestinal permeability via metabolomic analysis has utility in the early detection of diseases caused by an intestinal barrier breach.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"72"},"PeriodicalIF":3.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive profiling of folates across polyglutamylation and one-carbon states.","authors":"Sevcan Erşan, Yu Chen, Junyoung O Park","doi":"10.1007/s11306-025-02269-5","DOIUrl":"10.1007/s11306-025-02269-5","url":null,"abstract":"<p><strong>Introduction: </strong>One-carbon metabolism is central to carbon fixation, methylation, and biosynthesis of amino acids, lipids, and nucleotides. Folates are organic cofactors that harbor one-carbon units and shunt them across these metabolic pathways. Despite its essentiality to all life forms, the diverse nature of folate species with various polyglutamylation and one-carbon states makes their measurement challenging.</p><p><strong>Objectives: </strong>We aim to illuminate one-carbon metabolism by streamlining comprehensive profiling of folate polyglutamates.</p><p><strong>Methods: </strong>We analyze folate standards and cellular extracts containing diverse folates species by liquid chromatography-mass spectrometry (LC-MS).</p><p><strong>Results: </strong>We observe that Escherichia coli cells possess diverse folate polyglutamates with one to ten terminal glutamates. Interestingly, most folate polyglutamates form doubly charged ions as well as singly charged ions in LC-MS. Folates also undergo in-source fragmentation. The disparate fates of folates in MS make their quantitation prone to underestimation. Fragmentation by in-source collision-induced dissociation (CID) and LC separation circumvent this issue and facilitate robust and sensitive quantification of folates. In-source CID of folates generates reporter fragment ions that yield higher signals in the mass-to-charge ratio (m/z) range near the maximal mass resolution of Orbitrap MS. Our LC methods complement MS by effectively separating folates based on their polyglutamylation and one-carbon states.</p><p><strong>Conclusion: </strong>Our metabolomics approach tailored to folate polyglutamates reveals multiple layers of one-carbon metabolism organized by the lengths of polyglutamate tails in folates. Our analytical workflow is broadly applicable to folate profiling across various cell types to advance our knowledge of one-carbon metabolism as well as biotechnology and medicine.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"71"},"PeriodicalIF":3.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic signature of COVID-19 progression: potential prognostic markers for severity and outcome.","authors":"Hien Thi Thu Nguyen, Malene Pontoppidan Stoico, Vang Quy Le, Jakob Holm Dalsgaard Thomsen, Kasper Bygum Krarup, Karoline Assifuah Kristjansen, Inge Søkilde Pedersen, Henrik Bygum Krarup","doi":"10.1007/s11306-025-02264-w","DOIUrl":"10.1007/s11306-025-02264-w","url":null,"abstract":"<p><strong>Introduction: </strong>There are significant challenges remain in accurately categorizing the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients.</p><p><strong>Objectives: </strong>We used an untargeted 1H NMR-based metabolomics to assess the metabolomic changes in serum samples from a Danish cohort of 106 COVID-19-infected patients with mild to fatal disease courses and from patients with fatal outcomes from other diseases.</p><p><strong>Methods: </strong>In total, 240 serum samples were used for this study. We used the data for multiple analyses (1) to construct a predictive model for disease severity and outcome, (2) to identify prognostic markers for subsequent disease severity and outcome, and (3) to understand the disease consequences in the metabolome and how recovery or death is reflected in the altered biological pathways.</p><p><strong>Results: </strong>Our results revealed distinct alterations in the serum metabolome that could differentiate patients with COVID-19 by severity (mild or severe) or outcome (death or survival). Using receiver operating characteristic (ROC) curve analysis and four machine learning algorithms (random forest, linear support vector machine, PLS-DA, and logistic regression), we identified two biomarker sets with relevant biological functions that predict subsequent disease severity and patient outcome. The range of these severity-associated biomarkers was equally broad and included inflammatory markers, amino acids, fluid balance, ketone bodies, glycolysis-related metabolites, lipoprotein particles, and fatty acid levels.</p><p><strong>Conclusions: </strong>Our data suggest the potential benefits of broader testing of these metabolites from newly diagnosed patients to predict which COVID-19 patients will progress to severe disease and which patients will manifest severe symptoms to minimize mortality.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"70"},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver metabolomic profiles of sea lamprey (Petromyzon marinus) are influenced by sex and maturation stages.","authors":"Sonam Tamrakar, Belinda Huerta, Yu-Wen Chung-Davidson, Weiming Li","doi":"10.1007/s11306-025-02266-8","DOIUrl":"10.1007/s11306-025-02266-8","url":null,"abstract":"<p><strong>Introduction: </strong>Sea lamprey (Petromyzon marinus) is a unique vertebrate model to examine how liver metabolomes support different reproductive functions. Juvenile sea lamprey prey on other fish species by attaching to their body and feeding on their blood and body fluids. Once reaching adulthood, they cease feeding, migrate to spawning streams and begin their final sexual maturation. During these processes, the male livers produce large quantities of bile acid pheromone precursors to be modified and released via gills, whereas the female livers synthesize vast amounts of vitellogenin (yolk lipophosphoprotein) to be transported to the ovary.</p><p><strong>Objective: </strong>We aim to test the hypothesis that the liver metabolic pathways exhibit dramatic changes during sexual maturation of sea lampreys that support their reproductive strategies.</p><p><strong>Methods: </strong>Liver tissues from prespermiating (PSM) and spermiating (SM) males, and preovulatory (POF) and ovulatory (OF) females were homogenized, extracted and analyzed using the Thermo Q-exactive Orbitrap UPLC/MS/MS. Progenesis QI, Compound Discoverer, and Metaboanalyst were used for alignment, peak picking, deconvolution, and annotation. Data were subjected to analyses such as PCA and PLS-DA, using the SIMCA® software. The glycogen and triglyceride content in liver were also examined to determine levels of stored energy.</p><p><strong>Results: </strong>Overall, we found upregulations of amino acid and fatty acid metabolisms in mature male sea lamprey compared to the immature ones. Although the metabolic differences were comparatively subdued in the sexually immature males and females, amino acid regulation was slightly higher in females.</p><p><strong>Conclusion: </strong>We conclude that the metabolic dynamics in sea lamprey livers are consistent with their reproductive strategies.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"69"},"PeriodicalIF":3.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A narrative review of metabolomics approaches in identifying biomarkers of doxorubicin-induced cardiotoxicity.","authors":"Amarnath Singh, Maham Bakhtyar, Se-Ran Jun, Marjan Boerma, Renny S Lan, L Joseph Su, Sam Makhoul, Ping-Ching Hsu","doi":"10.1007/s11306-025-02258-8","DOIUrl":"10.1007/s11306-025-02258-8","url":null,"abstract":"<p><strong>Background: </strong>While anthracyclines, commonly used in cancer treatment, are well known to cause cardiotoxicity, no validated biomarkers currently exist that can predict the early development of doxorubicin-induced cardiotoxicity (DIC). Therefore, identifying early biomarkers of DIC is urgently needed. Metabolomics approaches have been used to elucidate this relationship and identified related metabolite markers. However, differences in pre-clinical model systems make it challenging to draw definitive conclusions from the discoveries and translate findings into clinical applications.</p><p><strong>Aim of review: </strong>A systematic literature search on metabolomics studies of DIC was conducted with the goal to identify and compare study results reported using in vitro models, animal models, and studies from clinical patients. Metabolites identified across all studies were pooled to uncover biologically meaningful patterns that are significantly enriched in the data. Finally, pooled metabolites perturbed by DIC were mapped to metabolic pathways to explore potential pathological implications.</p><p><strong>Results: </strong>We reviewed 28 studies published between 2000 and 2024 that utilized metabolomics approaches to investigate DIC. The included studies used a variety of analytical techniques, including LC-MS, GC-MS, and NMR. The analysis revealed that metabolites such as inosine, phenylalanine, arginine, and tryptophan were commonly perturbed across all study models, with carnitine metabolism and purine and pyrimidine metabolism being the most affected pathways. Metabolite Set Enrichment Analysis (MSEA) using MetaboAnalyst identified the arginine biosynthesis, citrate cycle, and alanine, aspartate, and glutamate metabolism pathways as significantly enriched.</p><p><strong>Conclusion: </strong>These findings underscore the potential of metabolomics in identifying early biomarkers for DIC, providing a foundation for future studies aimed at preventing cardiotoxicity and improving treatment strategies for cancer patients receiving DOX-containing therapies.</p><p><strong>Key scientific concepts of review: </strong>Altogether, metabolomics studies suggest metabolic alterations in DIC, albeit little overlap between studies especially with animal and human studies. Attempts at intercepting these pathways have shown that intervention in DIC may be possible. Future research should focus on developing precise cardiotoxicity models that incorporate cancer metabolism, as these will be crucial in bridging the gap between laboratories (in vitro and animal models) and clinical studies to identify subclinical biomarkers in the early stage of DIC that can effectively identify new targets for interventions to reduce lethal cardiovascular disease risk.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"68"},"PeriodicalIF":3.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics: a new frontier in neurodegenerative disease biomarker discovery.","authors":"Krishan Kumar Verma, Praveen Kumar Gaur, Sonia Lal Gupta, Kanak Lata, Rahul Kaushik, Vikas Sharma","doi":"10.1007/s11306-025-02267-7","DOIUrl":"https://doi.org/10.1007/s11306-025-02267-7","url":null,"abstract":"<p><strong>Background: </strong>Neurodegenerative disorders are a group of debilitating diseases affecting the central nervous system, and are characterized by the progressive loss of neurons, leading to declines in cognitive function, movement, and overall quality of life. While the exact causes remain elusive, it's believed that a combination of genetic, environmental, and lifestyle factors contribute to their development. Metabolites, the end products of cellular processes, reflect the physiological state of an organism. By analysing these molecules, researchers can gain a deeper understanding of the underlying metabolic changes associated with neurodegenerative disorders.</p><p><strong>Aim of review: </strong>This review aims to explore the possibilities between metabolites and their association with neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS) and Huntington's disease (HD).</p><p><strong>Key scientific concepts of review: </strong>Metabolomic studies could potentially illuminate altered biochemical pathways, facilitating earlier detection and treatment of these conditions. Metabolomic investigations have revealed the role of oxidative stress, alterations in glucose and fat metabolism, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and alterations in myelin composition in neurodegenerative disorders. The common metabolic biomarkers identified includes glutamate, taurine, uric acid, branched chain amino acids, acylcarnitine, creatinine, choline, with some more amino acids and lipids. Metabolomics offers valuable insights into disease mechanisms and potential therapeutic targets by identifying biochemical and metabolic alterations, but still there are several aspects to be explored for accurate mapping of metabolites with specific pathway involved in the disease.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"67"},"PeriodicalIF":3.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recommendations for sample selection, collection and preparation for NMR-based metabolomics studies of blood.","authors":"Abdul-Hamid Emwas, Helena U Zacharias, Marcos Rodrigo Alborghetti, G A Nagana Gowda, Daniel Raftery, Ryan T McKay, Chung-Ke Chang, Edoardo Saccenti, Wolfram Gronwald, Sven Schuchardt, Roland Leiminger, Jasmeen Merzaban, Nour Y Madhoun, Mazhar Iqbal, Rawiah A Alsiary, Rupali Shivapurkar, Arnab Pain, Dhanasekaran Shanmugam, Danielle Ryan, Raja Roy, Horst Joachim Schirra, Vanessa Morris, Ana Carolina Zeri, Fatimah Alahmari, Rima Kaddurah-Daouk, Reza M Salek, Marcia LeVatte, Mark Berjanskii, Brian Lee, David S Wishart","doi":"10.1007/s11306-025-02259-7","DOIUrl":"https://doi.org/10.1007/s11306-025-02259-7","url":null,"abstract":"<p><strong>Background: </strong>Metabolic profiling of blood metabolites, particularly in plasma and serum, is vital for studying human diseases, human conditions, drug interventions and toxicology. The clinical significance of blood arises from its close ties to all human cells and facile accessibility. However, patient-specific variables such as age, sex, diet, lifestyle and health status, along with pre-analytical conditions (sample handling, storage, etc.), can significantly affect metabolomic measurements in whole blood, plasma, or serum studies. These factors, referred to as confounders, must be mitigated to reveal genuine metabolic changes due to illness or intervention onset.</p><p><strong>Review objective: </strong>This review aims to aid metabolomics researchers in collecting reliable, standardized datasets for NMR-based blood (whole/serum/plasma) metabolomics. The goal is to reduce the impact of confounding factors and enhance inter-laboratory comparability, enabling more meaningful outcomes in metabolomics studies.</p><p><strong>Key concepts: </strong>This review outlines the main factors affecting blood metabolite levels and offers practical suggestions for what to measure and expect, how to mitigate confounding factors, how to properly prepare, handle and store blood, plasma and serum biosamples and how to report data in targeted NMR-based metabolomics studies of blood, plasma and serum.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"66"},"PeriodicalIF":3.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise intensity determines circulating levels of Lac-Phe and other exerkines: a randomized crossover trial.","authors":"Dirk Weber, Paola G Ferrario, Achim Bub","doi":"10.1007/s11306-025-02260-0","DOIUrl":"10.1007/s11306-025-02260-0","url":null,"abstract":"<p><strong>Introduction: </strong>Exercise metabolomics research has revealed significant exercise-induced metabolic changes and identified several exerkines as mediators of physiological adaptations to exercise. However, the effect of exercise intensity on metabolic changes and circulating exerkine levels remains to be examined.</p><p><strong>Objectives: </strong>This study compared the metabolic responses to moderate-intensity and vigorous-intensity aerobic exercise.</p><p><strong>Methods: </strong>A two-period crossover trial was conducted under controlled conditions at the Max Rubner-Institute in Karlsruhe, Germany. Seventeen young, healthy, and physically active men performed 30 min moderate-intensity (50% VO_2peak) and vigorous-intensity (75% VO_2peak) aerobic exercise using two bicycle ergometer protocols in a randomized sequence. Blood samples obtained immediately before exercise and at four time points after exercise were analyzed in an untargeted metabolomics approach, and separate linear mixed models were applied to over 1000 metabolites.</p><p><strong>Results: </strong>Vigorous-intensity exercise induced a greater metabolic response than moderate-intensity exercise. Several intensity-dependent metabolites were identified, primarily involved in amino acid metabolism and energy conversion pathways, including N-lactoyl-amino acids, TCA cycle intermediates, N-acetylated amino acids, and acylcholines. The exerkines N-lactoyl-phenylalanine, lactate, and succinate were among the most intensity-dependent metabolites. N-acetylated amino acids and acylcholines were systematically altered by exercise intensity, indicating potential physiological functions.</p><p><strong>Conclusion: </strong>Exercise intensity significantly affects exercise-induced metabolic alterations and changes in exerkine levels. Our results expand the knowledge about exerkine dynamics and emphasize the role of exercise intensity in promoting physiological adaptations to exercise. The trial was registered on October 5, 2017, at the German Clinical Trials Register under the Registration Number DRKS00009743 (Universal Trial Number of WHO: U1111-1200-2530).</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"63"},"PeriodicalIF":3.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing limonene production by probing the metabolic network through time-series metabolomics data.","authors":"Jasmeet Kaur Khanijou, Clement P M Scipion, Shreyash Borkar, Xixian Chen, Wee Chew","doi":"10.1007/s11306-025-02254-y","DOIUrl":"https://doi.org/10.1007/s11306-025-02254-y","url":null,"abstract":"<p><strong>Introduction: </strong>Limonene is a monoterpene with diverse applications in food, medicine, fuel, and material science. Recently, engineered microbes have been used to biosynthesize target biochemicals such as limonene.</p><p><strong>Objective: </strong>Metabolic engineering has shown that factors such as feedback inhibition, enzyme activity or abundance may contribute to the loss of target biochemicals. Incorporating a hypothesis driven experimental approach can help to streamline the process of improving target yield.</p><p><strong>Method: </strong>In this work, time-series intracellular metabolomics data from Escherichia coli cultures of a wild-type strain engineered to overproduce limonene (EcoCTs3) was collected, where we hypothesized having more carbon flux towards the engineered mevalonate (MEV) pathway would increase limonene yield. Based on the topology of the metabolic network, the pathways involved in mixed fermentation were possibly causing carbon flux loss from the MEV pathway. To prove this, knockout strains of lactate dehydrogenase (LDH) and aldehyde dehydrogenase-alcohol dehydrogenase (ALDH-ADH) were created.</p><p><strong>Results: </strong>The knockout strains showed 18 to 20 folds more intracellular mevalonate accumulation over time compared to the EcoCTs3 strain, thus indicating greater carbon flux directed towards the MEV pathway thereby increasing limonene yield by 8 to 9 folds.</p><p><strong>Conclusion: </strong>Ensuring high intracellular mevalonate concentration is therefore a good strategy to enhance limonene yield and other target compounds using the MEV pathway. Once high intracellular mevalonate concentration has been achieved, the limonene producing strain can then be further modified through other strategies such as enzyme and protein engineering to ensure better conversion of mevalonate to downstream metabolites to produce the target product limonene.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"61"},"PeriodicalIF":3.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal lipoprotein and inflammatory mediators analysis uncover persisting inflammation and hyperlipidemia following SARS-CoV-2 infection in long COVID-19.","authors":"Gyuntae Bae, Zhiqi Yang, Daniele Bucci, Claire Wegner, Hartmut Schäfer, Yogesh Singh, Caterina Lonati, Christoph Trautwein","doi":"10.1007/s11306-025-02262-y","DOIUrl":"https://doi.org/10.1007/s11306-025-02262-y","url":null,"abstract":"<p><strong>Introduction: </strong>Individuals suffering from acute COVID-19 (AC) often develop long COVID-19 (LC) syndrome that is associated with aberrant levels of lipoproteins and inflammatory mediators. Yet, these dysregulations are heterogenous due to the uncertain prevalence and require a more extensive characterization.</p><p><strong>Objectives: </strong>This study aimed to investigate LC-associated dysregulations in inflammatory mediators and lipids by longitudinal Nuclear Magnetic Resonance (NMR) lipoprotein analysis and cytokine profiling in human blood.</p><p><strong>Methods: </strong>We quantitatively profiled lipoproteins and inflammatory parameters in LC patients at 5 (n = 95), 9 (n = 73), 12 (n = 95), 16 (n = 78), and 20 (n = 85) months post AC by in vitro diagnostics research (IVDr)-based NMR spectroscopy. Simultaneously, we assessed inflammatory meditators with a 13-plex cytokine panel by flow cytometry. We then compared the lipoprotein profiles with historical data from AC (N = 307) and healthy cohorts collected before the COVID-19 pandemic (N = 305), whereas the cytokine profiles were correlated with that of the AC cohort.</p><p><strong>Results: </strong>We identified 31 main and 80 significantly altered subclass lipoproteins, respectively. LC was associated with higher serum levels of very low-density, intermediate-density, low-density, high-density lipoproteins, along with triglycerides, cholesterols, and apolipoprotein a-I & a-II lipoproteins compared to the healthy cohort. We also observed significantly lower concentrations of NMR-based inflammatory parameters in LC than in AC cohort, whilst proinflammatory mediators IFN-α2, IFN-γ, TNF-α, CXCL8/IL-8, IL-12p70, IL-17 A, and IL-23 displayed significantly higher concentrations in LC compared with the AC cohort. Conversely, CCL2/MCP-1, IL-6, and IL-18 were significantly higher in the AC cohort than in LC.</p><p><strong>Conclusion: </strong>Our findings demonstrate a persistent hyperlipidemic phenotype in LC alongside signs of chronic inflammation and lipoprotein metabolism that vary in states of acute and chronic inflammation.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"65"},"PeriodicalIF":3.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}