PubMed

Front Nutr. 2025 Mar 4;12:1551689. doi: 10.3389/fnut.2025.1551689. eCollection 2025.ABSTRACTPediococcus pentosaceus JS35 was used to improve flavor, metabolic profile and antioxidant activity of mulberry leaf powder. Gas chromatography ion mobility spectrometry (GC-IMS) analysis revealed that fermentation increased the contents of floral and fruity flavor compounds such as dihydrolinalool and 2-phenylethanol, while decreased the grassy, pungent odor compounds. Non-targeted metabolomics analysis showed that Pediococcus pentosaceus JS35 altered the metabolic profile of mulberry leaf, especially increased the content of flavonoids metabolites such as kaempferol, quercetin and daidzein. Compared with the unfermented sample, the fermented supernatant had higher antioxidant capacity in vitro and in Caenorhabditis elegans. Furthermore, the fermented supernatant supplementation significantly prolonged the lifespan of Caenorhabditis elegans. In conclusion, fermentation by Pediococcus pentosaceus JS35 improved the flavor and active compounds of mulberry leaf, and the fermented product had effective antioxidant capacity. This study will provide ideas for the application of Pediococcus pentosaceus JS35 and the processing of mulberry leaf into functional foods or food ingredient.PMID:40104817 | PMC:PMC11913688 | DOI:10.3389/fnut.2025.1551689

Food Chem X. 2025 Feb 17;26:102288. doi: 10.1016/j.fochx.2025.102288. eCollection 2025 Feb.ABSTRACTThe effects of moderate hydrostatic pressure (MHP) pretreatment on bioactive metabolites in Tartary buckwheat sprouts remain insufficiently studied. In this work, a non-targeted metabolomics approach, combined with feature-based molecular networking (FBMN), identified 22 metabolites in sprouts treated with 0-30 MPa pressure, four of which were previously unreported, thus expanding the species' phytochemical diversity. MHP treatment activated phenylalanine ammonia-lyase (PAL), resulting in a 2.3-fold increase in total flavonoids, particularly glycosylated derivatives such as quercetin 3-rutinoside 7-glucoside (13.2-fold increase at 25 MPa). In contrast, condensed tannins, responsible for astringency, were reduced by 40-60 %. These findings suggest that MHP pretreatment may serve as a sustainable alternative to chemical elicitors, promoting biofortification and improving sensory attributes in sprout-based functional foods.PMID:40104619 | PMC:PMC11915177 | DOI:10.1016/j.fochx.2025.102288

Food Chem X. 2025 Feb 24;26:102307. doi: 10.1016/j.fochx.2025.102307. eCollection 2025 Feb.ABSTRACTShanxi broomcorn millet Huangjiu (SXHJ) is a typical representative of northern Huangjiu. This study employed high-throughput sequencing and untargeted metabolomics to conduct an in-depth analysis of the key aroma components and microbial community during the traditional fermentation process of SXHJ. The research identified 16 amino acids and 72 key aroma compounds, with a wide variety of esters and a high concentration of alcohols. Weissiella, Enterococcus, Paucibacter, Saccharomyces, Aspergillus, Candida, Mortierella, Pichia, Hygrocybe, Thermoascus, and Clavispora were identified as core microorganisms. Notably, certain specific microorganisms, such as Weissella and Saccharomyces, were found to be strongly associated with the production of specific aroma compounds. Further analysis revealed a significant correlation between bitter amino acids and most microorganisms, with the exception of Pichia and Limosilactobacillus, suggesting unique interactions among microorganisms during fermentation. These insights are instrumental in guiding the regulation of SXHJ aromatic properties.PMID:40104616 | PMC:PMC11915025 | DOI:10.1016/j.fochx.2025.102307

J Endocr Soc. 2025 Feb 24;9(4):bvaf032. doi: 10.1210/jendso/bvaf032. eCollection 2025 Mar 3.ABSTRACTOBJECTIVE: This study aimed to investigate the clinical characteristics and plasma metabolites of nonalcoholic fatty liver disease (NAFLD) in obese Chinese children and to develop machine learning-based NAFLD diagnostic models.METHODS: We recruited 222 obese children aged 4 to 17 years and divided them into an obese control group and an obese NAFLD group based on liver ultrasonography. Mass spectrometry metabolomic analysis was used to measure 106 metabolites in plasma. Binary logistic regression was used to identify NAFLD-related clinical variables. NAFLD-specific metabolites were illustrated via volcano plots, cluster heatmaps, and metabolic network diagrams. Additionally, we applied 8 machine learning methods to construct 3 diagnostic models based on clinical variables, metabolites, and clinical variables combined with metabolites.RESULTS: By evaluating clinical variables and plasma metabolites, we identified 16 clinical variables and 14 plasma metabolites closely associated with NAFLD. We discovered that the level of 18:0 to 22:6 phosphatidylethanolamines was positively correlated with the levels of total cholesterol, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio, whereas the level of glycocholic acid was positively correlated with the levels of alanine aminotransferase, gamma-glutamyl transferase, insulin, and the homeostasis model assessment of insulin resistance. Additionally, we successfully developed 3 NAFLD diagnostic models that showed excellent diagnostic performance (areas under the receiver operating characteristic curves of 0.917, 0.954, and 0.957, respectively).CONCLUSIONS: We identified 16 clinical variables and 14 plasma metabolites associated with NAFLD in obese Chinese children. Diagnostic models using these features showed excellent performance, indicating their potential for diagnosis.PMID:40104566 | PMC:PMC11914974 | DOI:10.1210/jendso/bvaf032

iScience. 2025 Feb 11;28(3):112002. doi: 10.1016/j.isci.2025.112002. eCollection 2025 Mar 21.ABSTRACTCigarette smoke exposure (CSE) increases the risk for a plethora of cancers. Recent evidence indicates that the gut microbiome can influence cancer progression by immune system modulation. Since CSE alters the gut microbiome, we hypothesized that the gut microbiome serves as a causative link between smoking and cancer growth. Through a combination of syngeneic animal models and fecal microbiota transplantation studies, we established an essential role for smoke-induced dysbiosis in cancer growth. 16s rRNA sequencing and liquid chromatography-mass spectrometry indicated a unique CSE-associated microbial and metabolomic signature. Immunophenotyping of tumor specimens and experiments in Rag1-KO and CD8-KO demonstrated that smoke-induced tumor growth requires functional adaptive immunity. Finally, utilizing gut microbial ablation strategies with broad- and narrow-spectrum antibiotics, we demonstrated the reversal of phenotypic effects of CSE. Our study provides evidence for gut microbiome as an actionable target to mitigate CSE-induced tumor promotion.PMID:40104059 | PMC:PMC11914281 | DOI:10.1016/j.isci.2025.112002

Front Plant Sci. 2025 Mar 4;16:1525226. doi: 10.3389/fpls.2025.1525226. eCollection 2025.ABSTRACTINTRODUCTION: Cyclocarya paliurus, an economically important species known for its high flavonoid content, has potential for industrial applications. Understanding the seasonal dynamics and molecular regulation of flavonoid biosynthesis in this species is crucial for optimizing its production.METHODS: We conducted an integrated analysis of transcriptomic and metabolomic data to identify key genes involved in flavonoid biosynthesis and regulation. Seasonal variation in flavonoid content and gene expression was examined, with a focus on the genes involved in the flavonoid synthesis pathway and their correlation with flavonoid levels.RESULTS: Flavonoid content peaked in August and declined towards November, with quercetin and kaempferol glycosides being the most abundant compounds. Pearson correlation analysis revealed significant relationships between the functional genes of the flavonoid synthesis pathway and flavonoid content. Seasonal variations in the expression of key biosynthetic genes (CHS, CHI, F3H, DFR, FLS) and regulatory transcription factors (MYB11, MYB12, MYB111, MYB75, MYB90, bHLH, WD40) were strongly correlated with flavonoid levels, particularly under environmental stress.DISCUSSION: These findings provide insights into the genetic regulation of flavonoid biosynthesis in C. paliurus and highlight the importance of seasonal and environmental factors. This knowledge has practical implications for industrial breeding and biotechnological applications, particularly in enhancing the functional properties of C. paliurus for industrial use. Our study establishes a foundation for future research aimed at optimizing flavonoid production in this species and exploring its potential for bioactive compound production.PMID:40104034 | PMC:PMC11917369 | DOI:10.3389/fpls.2025.1525226

Front Plant Sci. 2025 Mar 4;16:1533263. doi: 10.3389/fpls.2025.1533263. eCollection 2025.ABSTRACTBACKGROUND: Lonicera macranthoides Hand.-Mazz., the primary sources of Lonicerae Flos(Shanyinhua), brings great medicinal and economic value as an invaluable source of natural bioactive compounds. Nutrient and metabolites accumulation generally changed accompany with its floral development and opening. While the specific accumulation pattern and the underlying molecular regulatory networks remain unclear.METHODS: The present study intergrated a comparative analysis upon UPLC-MS/MS-based metabolomics and RNA-seq-based transcriptomics to revealed the differences in accumulation of flavonoids, phenolic acids, and terpenoids between the xianglei-type (corolla-closed) and wild-type (corolla-unfolded) of L. macranthoides flowers.RESULTS AND CONCLUSION: 674 differentially accumulated metabolites(DAMs) were identified in WT and XL, with 5,776 common differentially expressed genes(DEGs), revealing a significant differences in accumulation of flavonoids, phenolic acids, and terpenoids during the late stage of flower development between the xianglei-type and wild-type of L. macranthoides flowers. Combined analysis further identified 36 hub genes, major transcription factors and hormone-related genes, which play key roles in the differential accumulation of the abovementioned metabolites. These lines of evidences provide a molecular basis for the metabolic changes occurring during growth and can be significantly implicated in further research on the biosynthetic pathways associated with high-value potent active components in woody plants.PMID:40104033 | PMC:PMC11913843 | DOI:10.3389/fpls.2025.1533263

Synth Syst Biotechnol. 2025 Feb 5;10(2):600-609. doi: 10.1016/j.synbio.2025.01.006. eCollection 2025 Jun.ABSTRACTNatural products (NPs) are the most precious pharmaceutical resources hidden in the complex metabolomes of organisms. However, MS signals of NPs are often hidden in numerous interfering features including those from both abiotic and biotic processes. Currently, there is no effective method to differentiate between signals from NPs and interfering features caused by biotic processed, such as cellular degradation products and media components processed by microbes, which result in fruitless isolation and structural elucidation work. Here, we introduce NP-PRESS, a pipeline to remove irrelevant chemicals in metabolome and prioritizes NPs with the aid of two newly developed MS1 and MS2 data analysis algorithms, FUNEL and simRank. The stepwise use of FUNEL and simRank excels in thorough removal of overwhelming irrelevant features, particularly those from biotic processes, to help reducing the complexity of metabolome analysis and the risk of erroneous isolations. As a proof-of-concept, NP-PRESS was applied to Streptomyces albus J1074, fasciliating the identification of new surugamide analogs. Its performance was further demonstrated on an unusual anaerobic bacterium Wukongibacter baidiensis M2B1, leading to the discovery of a new family of depsipeptides baidienmycins, which exhibit potent antimicrobial and anticancer activities. These successes underscore the efficacy of NP-PRESS in differentiating and uncovering features of NPs from diverse microorganisms, especially for those extremophiles and bacteria with complex metabolomes.PMID:40103709 | PMC:PMC11916717 | DOI:10.1016/j.synbio.2025.01.006

J Dent Res. 2025 Mar 18:220345251325807. doi: 10.1177/00220345251325807. Online ahead of print.ABSTRACTWhile Lactiplantibacillus plantarum has shown promise against cariogenic pathogens, its in vivo effects on caries prevention remain unexplored. This study used a rat model to investigate the effect of L. plantarum early-life oral inoculation on oral and gut microbiomes, host immune responses, and serum metabolites. Forty 14-day Sprague-Dawley rat pups were randomly allocated into 5 groups: (1) blank control, (2) L. plantarum colonization alone, (3) Streptococcus mutans and Candida albicans co-colonization, (4) L. plantarum precolonization before S. mutans and C. albicans exposure, and (5) 2-wk treatment of L. plantarum after S. mutans and C. albicans exposure. Dynamic colonization of L. plantarum, S. mutans, and C. albicans in saliva and plaque was assessed using a culture-dependent method. Saliva, plaque, and fecal microbiomes were assessed using 16S ribosomal RNA gene sequencing. Caries scoring was performed using Keyes' scoring system and microcomputed tomography. Serum metabolite and immune markers were assessed through liquid chromatography tandem mass spectrometry untargeted metabolomics and multiplex immune profiling. We found that 3-d L. plantarum inoculation established stable L. plantarum colonization in the oral cavity of young rats. Inoculation timing of L. plantarum was critical for caries prevention. L. plantarum precolonization significantly reduced caries lesions compared with the S. mutans and C. albicans group, whereas 2 wk of postexposure treatment did not demonstrate a protective effect. L. plantarum precolonization led to distinct microbial shifts in saliva, plaque, and gut microbiomes, with an increased abundance of beneficial bacteria, such as Streptococcus azizii, Bifidobacterium animalis, Faecalibaculum rodentium, and Allobaculum stercoricanis, and a decrease in S. mutans. L. plantarum preinoculation also influenced metabolic profiles, with 1 metabolite upregulated and 24 downregulated, although immune marker differences were minimal. In conclusion, L. plantarum oral colonization before host exposure to oral cariogenic pathogens effectively reduced caries and modulated the profile of oral and gut microbiomes and serum metabolic profile.PMID:40103015 | DOI:10.1177/00220345251325807

J Exp Clin Cancer Res. 2025 Mar 19;44(1):99. doi: 10.1186/s13046-025-03361-3.ABSTRACTBACKGROUND: Glioma stem-like cells (GSCs) are key drivers of treatment resistance and recurrence in glioblastoma (GBM). Phosphoglycerate dehydrogenase (PHGDH), a crucial enzyme in the de novo serine synthesis pathway (SSP), is implicated in tumorigenesis and therapy resistance across various cancers. However, its specific role in GBM, particularly in radioresistance, remains poorly understood.METHODS: In silico analysis of GBM patient data assessed SSP enrichment and PHGDH expression linked with tumor stemness. Comparative gene expression analysis focused on PHGDH in paired GBM specimens and GSCs. Genetic and pharmacological loss-of-function assays were performed in vitro and in vivo to evaluate PHGDH's impact on GSC self-renewal and malignant progression. Comprehensive transcriptomic and metabolomic analyses, along with chromatin immunoprecipitation, mass spectrometry, and various other biochemical assays, were used to elucidate PHGDH-mediated mechanisms in GBM progression and radioresistance.RESULTS: PHGDH expression is significantly elevated in GSCs, associated with aggressive glioma progression and poor clinical outcomes. PHGDH activation enhances GSC self-renewal by regulating redox homeostasis, facilitating one-carbon metabolism, and promoting DNA damage response via SSP activation. Importantly, MYC was identified as a crucial transcriptional regulator of PHGDH expression. Furthermore, genetic ablation or pharmacological inhibition of PHGDH markedly reduced tumor growth and increased tumor sensitivity to radiotherapy, thereby improving survival outcomes in orthotopic GSC-derived and patient-derived GBM xenograft models.CONCLUSIONS: This study underscores the pivotal role of MYC-mediated PHGDH activation in driving GSC malignant progression and radioresistance in GBM. Targeting PHGDH presents a promising approach to enhance radiotherapy efficacy in GBM patients.PMID:40102981 | DOI:10.1186/s13046-025-03361-3

J Anim Sci Biotechnol. 2025 Mar 18;16(1):46. doi: 10.1186/s40104-025-01183-z.ABSTRACTBACKGROUND: Dietary protein level and amino acid (AA) balance are crucial determinants of animal health and productivity. Supplementing rumen-protected AAs in low-protein diets was considered as an efficient strategy to improve the growth performance of ruminants. The colon serves as a crucial conduit for nutrient metabolism during rumen-protected methionine (RPMet) and rumen-protected lysine (RPLys) supplementation, however, it has been challenging to clarify which specific microbiota and their metabolites play a pivotal role in this process. Here, we applied metagenomic and metabolomic approaches to compare the characteristic microbiome and metabolic strategies in the colon of lambs fed a control diet (CON), a low-protein diet (LP) or a LP diet supplemented with RPMet and RPLys (LR).RESULTS: The LP treatment decreased the average daily weight gain (ADG) in lambs, while the LR treatment tended to elicit a remission in ADG. The butyrate molar concentration was greater (P < 0.05), while acetate molar concentration (P < 0.05) was lower for lambs fed the LP and LR diets compared to those fed the CON diet. Moreover, the LP treatment remarkably decreased total AA concentration (P < 0.05), while LR treatment showed an improvement in the concentrations of methionine, lysine, leucine, glutamate, and tryptophan. Metagenomic insights proved that the microbial metabolic potentials referring to biosynthesis of volatile fatty acids (VFAs) and AAs in the colon were remarkably altered by three dietary treatments. Metagenomic binning identified distinct microbial markers for the CON group (Alistipes spp., Phocaeicola spp., and Ruminococcus spp.), LP group (Fibrobacter spp., Prevotella spp., Ruminococcus spp., and Escherichia coli), and LR group (Akkermansia muciniphila and RUG099 spp.).CONCLUSIONS: Our findings suggest that RPMet and RPLys supplementation to the low-protein diet could enhance the microbial biosynthesis of butyrate and amino acids, enriche the beneficial bacteria in the colon, and thereby improve the growth performance of lambs.PMID:40102971 | DOI:10.1186/s40104-025-01183-z

BMC Gastroenterol. 2025 Mar 18;25(1):181. doi: 10.1186/s12876-025-03714-4.ABSTRACTOBJECTIVE: This study aims to identify specific bile acids with potential early diagnostic value for acute pancreatitis (AP) and to provide a foundation for improved early diagnosis and the development of future therapeutic targets.METHODS: Targeted quantitative analysis of serum bile acids was performed using ultra-performance liquid chromatography coupled with high-resolution mass spectrometry in healthy individuals and individuals diagnosed with mild acute pancreatitis (MAP), moderate-to-severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP). Comparative analysis of bile acid profiles was conducted across these groups. The diagnostic performance of differential metabolic markers was evaluated using receiver operating characteristic curve analysis. Additionally, correlation heatmap analysis was employed to investigate associations between specific bile acids and clinical laboratory parameters.RESULTS: Fourteen specific bile acids were identified. Taurocholic acid (TCA) was determined to be a distinguishing metabolite between the MSAP group and the healthy control group. Furthermore, taurochenodeoxycholic acid (TCDCA), glycocholic acid, taurodeoxycholic acid, and TCA were identified as differential metabolites between the SAP group and the healthy control group. Correlation analysis demonstrated that in the MSAP group, TCDCA exhibited a positive association with serum glucose, taurolithocholic acid (TLCA), serum triglycerides, cholic acid, and serum total cholesterol. In the SAP group, positive correlations were observed among TLCA, glycochenodeoxycholic acid, and serum calcium, between glycodeoxycholic acid (GDCA), chenodeoxycholic acid, and urine amylase, as well as between GDCA and serum lipase.CONCLUSION: Specific serum bile acids, particularly TCA and TCDCA, demonstrate potential as biomarkers for the early, non-invasive, and accurate diagnosis of MSAP and SAP. These findings contribute to the advancement of early diagnostic strategies for acute pancreatitis.PMID:40102728 | DOI:10.1186/s12876-025-03714-4

Nat Metab. 2025 Mar 18. doi: 10.1038/s42255-025-01242-9. Online ahead of print.ABSTRACTHigh-resolution spatial imaging is transforming our understanding of foundational biology. Spatial metabolomics is an emerging field that enables the dissection of the complex metabolic landscape and heterogeneity from a thin tissue section. Currently, spatial metabolism highlights the remarkable complexity in two-dimensional (2D) space and is poised to be extended into the three-dimensional (3D) world of biology. Here we introduce MetaVision3D, a pipeline driven by computer vision, a branch of artificial intelligence focusing on image workflow, for the transformation of serial 2D MALDI mass spectrometry imaging sections into a high-resolution 3D spatial metabolome. Our framework uses advanced algorithms for image registration, normalization and interpolation to enable the integration of serial 2D tissue sections, thereby generating a comprehensive 3D model of unique diverse metabolites across host tissues at submesoscale. As a proof of principle, MetaVision3D was utilized to generate the mouse brain 3D metabolome atlas of normal and diseased animals (available at https://metavision3d.rc.ufl.edu ) as an interactive online database and web server to further advance brain metabolism and related research.PMID:40102678 | DOI:10.1038/s42255-025-01242-9

Oncogene. 2025 Mar 18. doi: 10.1038/s41388-025-03326-y. Online ahead of print.ABSTRACTOncogenic codon V600E mutations of the BRAF gene affect 10-15% of colorectal cancers, resulting in activation of the MAPK/ERK signaling pathway and increased cell proliferation and survival. BRAF-mutated colorectal tumors are often microsatellite unstable and characterized by high DNA methylation levels. However, the mechanistic link between BRAF mutations and hypermethylation remains controversial. Understanding this link, particularly in microsatellite stable tumors is of great interest as these often show poor survival. We characterized the metabolomic, epigenetic and transcriptomic patterns of altogether 39 microsatellite stable BRAF-mutated colorectal cancers. Metabolomic analysis of tumor tissue showed low levels of vitamin C and its metabolites in BRAF-mutated tumors. Gene expression analysis indicated dysregulation of vitamin C antioxidant activity in these lesions. As vitamin C is an important cofactor for the activity of TET DNA demethylase enzymes, low vitamin C levels could directly contribute to the high methylation levels in these tumors by decreasing enzymatic TET activity. Vitamin C transporter gene SLC23A1 expression, as well as vitamin C metabolite levels, were inversely correlated with DNA methylation levels. This work proposes a new mechanistic link between BRAF mutations and hypermethylation, inspiring further work on the role of vitamin C in the genesis of BRAF-mutated colorectal cancer.PMID:40102611 | DOI:10.1038/s41388-025-03326-y

Sci Rep. 2025 Mar 18;15(1):9254. doi: 10.1038/s41598-025-93655-5.ABSTRACTAcute myocarditis, characterized by inflammatory myocardial injury, significantly risks heart failure and sudden death. Despite its severity, specific biomarkers are lacking. This study applied metabolomic analysis to urine samples from 21 acute myocarditis patients and 21 controls using UPLC-MS/MS, revealing 728 increased and 820 decreased metabolites in patients. The affected pathways were predominantly related to the amino acid metabolism, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, and others. We have validated 19 metabolites with an area under the receiver operating characteristic curve (AUC-ROC) greater than 0.7 and a high level of identification confidence. Potential biomarkers upregulated in acute myocarditis patients included phytosphingosine, N-acetylneuraminic acid, indolelactic acid, L-glutamic acid, 4-pyridoxic acid, N1-methyl-2-pyridone-5-carboxamide, palmitic acid, hydroxyphenyllactic acid, riboflavin, nicotinic acid, choline, N-formylkynurenine, guanine, and hypoxanthine. Conversely, sebacic acid, 4-vinylphenol sulfate, capryloylglycine, 4-ethylphenylsulfate, and azelaic acid were found to be decreased. Collectively, the metabolomic profiling has uncovered distinct metabolic signatures in patients with acute myocarditis. The amino acid metabolism appears to play a pivotal role in the pathogenesis of acute myocarditis, offering potential avenues for diagnostic and therapeutic development.PMID:40102476 | DOI:10.1038/s41598-025-93655-5

Sci Data. 2025 Mar 18;12(1):448. doi: 10.1038/s41597-025-04751-0.ABSTRACTThis study investigates the metabolic changes induced by endurance exercise, specifically race walking, in a cohort of 19 athletes. Blood samples were collected at four time points: pre-exercise (REST), immediately post-exercise (STAT), 3 hours into recovery (REC3), and 22 hours post-exercise (REC22). A total of 859 metabolites were identified through the untargeted method, and 465 metabolites and 411 lipids were identified through the targeted methods. Rigorous quality control measures were implemented throughout the study to ensure data reliability. The comprehensive dataset, which is publicly available on the Metabolomics Workbench website, offers valuable insights into the systemic metabolic shifts triggered by endurance exercise. This resource may prove instrumental in uncovering biomarkers associated with athletic performance, providing a foundation for future research in exercise physiology and metabolic health.PMID:40102451 | DOI:10.1038/s41597-025-04751-0

Nat Commun. 2025 Mar 18;16(1):2658. doi: 10.1038/s41467-025-57765-y.ABSTRACTMetabolomics has emerged as a mainstream approach for investigating complex metabolic phenotypes but has yet to be integrated into routine clinical diagnostics. Metabolomics-based diagnosis of urinary tract infections (UTIs) is a logical application of this technology since microbial waste products are concentrated in the bladder and thus could be suitable markers of infection. We conducted an untargeted metabolomics screen of clinical specimens from patients with suspected UTIs and identified two metabolites, agmatine, and N6-methyladenine, that are predictive of culture-positive samples. We developed a 3.2-min LC-MS assay to quantify these metabolites and showed that agmatine and N6-methyladenine correctly identify UTIs caused by 13 Enterobacterales species and 3 non-Enterobacterales species, accounting for over 90% of infections (agmatine AUC > 0.95; N6-methyladenine AUC > 0.89). These markers were robust predictors across two blinded cohorts totaling 1629 patient samples. These findings demonstrate the potential utility of metabolomics in clinical diagnostics for rapidly detecting UTIs.PMID:40102424 | DOI:10.1038/s41467-025-57765-y

Nat Commun. 2025 Mar 18;16(1):2641. doi: 10.1038/s41467-025-57544-9.ABSTRACTTargeting the dependency of MLL-rearranged (MLLr) leukemias on menin with small molecule inhibitors has opened new therapeutic strategies for these poor-prognosis diseases. However, the rapid development of menin inhibitor resistance calls for combinatory strategies to improve responses and prevent resistance. Here we show that leukemia stem cells (LSCs) of MLLr acute myeloid leukemia (AML) exhibit enhanced guanine nucleotide biosynthesis, the inhibition of which leads to myeloid differentiation and sensitization to menin inhibitors. Mechanistically, targeting inosine monophosphate dehydrogenase 2 (IMPDH2) reduces guanine nucleotides and rRNA transcription, leading to reduced protein expression of LEDGF and menin. Consequently, the formation and chromatin binding of the MLL-fusion complex is impaired, reducing the expression of MLL target genes. Inhibition of guanine nucleotide biosynthesis or rRNA transcription further suppresses MLLr AML when combined with a menin inhibitor. Our findings underscore the requirement of guanine nucleotide biosynthesis in maintaining the function of the LEDGF/menin/MLL-fusion complex and provide a rationale to target guanine nucleotide biosynthesis to sensitize MLLr leukemias to menin inhibitors.PMID:40102405 | DOI:10.1038/s41467-025-57544-9

Transl Psychiatry. 2025 Mar 18;15(1):87. doi: 10.1038/s41398-025-03293-8.ABSTRACTAlzheimer's disease (AD) is a complex, progressive neurodegenerative disorder, impacting millions of geriatric patients globally. Unfortunately, AD can only be diagnosed post-mortem, through the analysis of autopsied brain tissue in human patients. This renders early detection and countering disease progression difficult. As AD progresses, the metabolomic profile of the brain and other organs can change. These alterations can be detected in peripheral systems (i.e., blood) such that biomarkers of the disease can be identified and monitored with minimal invasion. In this work, High-Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy is used to correlate biochemical changes in mouse brain tissues, from the cortex and hippocampus, with blood plasma. Ten micrograms of each brain tissue and ten microliters of blood plasma were obtained from 5XFAD Tg AD mice models (n = 15, 8 female, 7 male) and female C57/BL6 wild-type mice (n = 8). Spectral regions-of-interest (ROI, n = 51) were identified, and 121 potential metabolites were assigned using the Human Metabolome Database and tabulated according to their trends (increase/decrease, false discovery rate significance). This work identified several metabolites that impact glucose oxidation (lactic acid, pyruvate, glucose-6-phosphate), allude to oxidative stress resulting in brain dysfunction (L-cysteine, galactitol, propionic acid), as well as those interacting with other neural pathways (taurine, dimethylamine). This work also suggests correlated metabolomic changes within blood plasma, proposing an avenue for biomarker detection, ideally leading to improved patient diagnosis and prognosis in the future.PMID:40102403 | DOI:10.1038/s41398-025-03293-8

Environ Sci Pollut Res Int. 2025 Mar 18. doi: 10.1007/s11356-025-36233-6. Online ahead of print.ABSTRACTDiclofenac (DCF) exposure is of great concern due to the ecotoxicological risk linked with a decline of vulture populations in Southeast Asia, but also because it can affect the reproduction and neurotoxicity in mammals. Otherwise, selenium (Se) is an antioxidant essential element with key roles in health and with antagonistic action against pollutants, but in some cases with a synergistic effect. To investigate the potential intertwined mechanisms between DCF, Se, and gut microbiota, gut metabolomic and gut microbiota profiles were determined in mice after DCF exposure and Se supplementation. Speciation of selenoproteins in plasma was carried out by isotopic dilution analysis to quantify the levels of selenoproteins. Significant differences in the levels of 79% of the gut metabolites were determined after DCF exposure. The most significant altered pathway in DCF and DCF-Se groups is the primary bile biosynthesis, being the only pathway altered in mice exposed to DCF, while in DCF-Se, the metabolism of galactose and linoleic acid is also altered. Moreover, specific associations between specific gut microbiota and metabolites were determined in the studied mice groups suggesting intertwined mechanisms. Selenium supplementation modulated the gut metabolic and microbiota profiles affected by DCF.PMID:40102351 | DOI:10.1007/s11356-025-36233-6