PubMed

Front Microbiol. 2025 Mar 5;16:1501068. doi: 10.3389/fmicb.2025.1501068. eCollection 2025.ABSTRACTSpleen deficiency is an important immune and digestive system change. Ergosterone (ER) is bioactive steroid; however, to date, no relevant studies have explored its potential efficacy in treating spleen deficiency. The aim of the present study was to investigate the therapeutic effects and mechanism of action of ER on spleen deficiency syndrome induced by Rhei Radix et Rhizoma (RRR). RRR was used to induce the development of a spleen deficiency rat model to observe changes in body weight and pathological changes in organ tissues. Additionally, the levels of relevant immune factors and gastrointestinal hormones were measured, as well as the expression of intestinal tight junction proteins and the P38MAPK signaling pathway. Changes in intestinal microbiota and metabolites were measured, and the effect of ER on the RRR-induced spleen deficiency rat model was evaluated. ER notably alleviated the symptoms of RRR-induced spleen deficiency induced in rats and offered protection against organ damage. Ergosterone can increase the expression of immunoglobulins, inhibits the increase in inflammatory factors, improve gastrointestinal hormone disorders, protect the intestinal mucosa, and repair intestinal barrier damage. The ER-treated group exhibited substantial upregulation of claudin and occludin mRNA and protein expression levels in the colonic tissue. Additionally, ER inhibited the P38MAPKsignaling pathway, thereby improving RRR induced spleen deficiency syndrome in rats. ER also influences the metabolic pathways of protein digestion and absorption, biosynthesis of unsaturated fatty acids, and arachidonic acid metabolism. In addition, ER can regulate and enhance the composition of intestinal flora in rats with spleen deficiency, increase the diversity of dominant flora, and inhibit the proliferation of harmful bacteria. ER can treat spleen deficiency syndrome by enhancing immune function, improving gastrointestinal function, repairing the intestinal barrier, and regulating intestinal flora and intestinal metabolites.PMID:40109979 | PMC:PMC11920137 | DOI:10.3389/fmicb.2025.1501068

Front Microbiol. 2025 Mar 5;16:1516685. doi: 10.3389/fmicb.2025.1516685. eCollection 2025.ABSTRACTOBJECTIVE: This study aims to assess the effects of Jidangga-7 on enhancing gut microbiota function in non-small cell lung cancer.MATERIALS AND METHODS: Eighteen mice were screened and randomly divided into three groups: a control group, a model group with induced non-small cell lung cancer, and a treatment group receiving Jidangga-7. A549 tumor cells were implanted in the mice, and tumor formation was monitored. Upon successful tumor induction, the treatment group received Jidangga-7 via oral gavage, while the other groups received an equivalent volume of saline. After the final dose, intestinal tissues were collected from each group, and microbial amplicon 16S analysis and non-extensive targeted metabolomics were employed to characterize intestinal fiber and associated metabolites.RESULTS: By quantifying the contribution of individual species to the variations between the groups, the Sipmer results highlighted the top 10 species and their abundance that contribute to the differences between the two groups. Specifically, Jidangga-7 demonstrated a regulatory effect on various taxa such as Gammaproteobacteria, Bacilli, and Desulfovovoviridae. At the family level, administration of Jidangga-7 exhibited a regulatory effect on families including Desulfovibrionaceae, Lachnospiraceae, and Eggerthellaceae, compared to the model group. In untargeted metabolomics analyses, principal component analysis effectively differentiated the groups from one another. Subsequently, metabolites with a variable importance in projection score > 1 were screened. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed 20 metabolite pathways, encompassing metabolism of cofactors and vitamins, bacterial metabolism, antimicrobial pathways, and xenobiotics biodegradation and metabolism.CONCLUSION: Jidangga-7 exerted a positive influence on the intestinal microbial environment in mice with non-small cell carcinoma, ameliorating the dysbiosis induced by non- small cell lung cancer. This intervention inhibited the growth of pathogenic bacteria while fostering the growth of beneficial strains.PMID:40109975 | PMC:PMC11919877 | DOI:10.3389/fmicb.2025.1516685

Front Microbiol. 2025 Mar 5;16:1548782. doi: 10.3389/fmicb.2025.1548782. eCollection 2025.ABSTRACTPullorum disease (PD) caused by Salmonella Pullorum (SP) results in high mortality in chicks and potential carriers in adult chickens, negatively affecting growth and egg production. This study identified SP infection in 100-day-old White Plymouth Rock hens by serum plate agglutination and fecal and anal swab polymerase chain reaction. SP-infected broilers were classified into positive (P) and negative (N) groups using hematoxylin-and-eosin staining, metabolome sequencing, and 16S rDNA to investigate the effects of SP infection on the metabolites and microorganisms in the cecum of broilers. Groups had different degrees of inflammatory cell infiltration in the cecum, spleen, liver, and lung tissues. The diversity of bacterial flora in the cecum of Groups P and N differed significantly (P < 0.05). o__Lactobacillales and o__Verrucomicrobiota were significantly higher in Group P than in Group N (P < 0.05). At the genus level, g__Akkermansia was significantly higher in Group N (P < 0.05). Metabolome sequencing of cecum contents in Groups P and N screened 77 differential metabolites at the secondary metabolite level. 11 metabolites, including 2,4-dimethylbenzaldehyde, 3a,6b,7b,12a-tetrahydroxy-5b-cholanoic acid, and LysoPG 19:1, were differentially expressed in Group P (P < 0.05). A combined analysis of 16S rDNA sequencing and cecal content metabolomics identified 28 genera significantly associated with 38 metabolites in the cecum (P < 0.05). Specific bacterial genera such as Corynebacterium and Roseobacter have particularly prominent effects on metabolites. These findings highlight the significant alterations in gut microbial composition and metabolic functions due to SP infection. The differential metabolites and bacterial taxa identified in this study may provide insights into the underlying mechanisms of PD pathogenesis and potential biomarkers for disease management.PMID:40109970 | PMC:PMC11920158 | DOI:10.3389/fmicb.2025.1548782

Front Microbiol. 2025 Mar 5;16:1500961. doi: 10.3389/fmicb.2025.1500961. eCollection 2025.ABSTRACTINTRODUCTION: This study was conducted to investigate the effects of compound polysaccharides (CP), composed of Astragalus polysaccharide and Poria cocos polysaccharide, on immunity, antioxidant capacity, gut microbiota, and serum metabolome in kittens.METHODS: A total of 14 4-month-old kittens, with an average body weight of 2.39 kg, were used in a 56-day experiment. They were randomly assigned to the control (CON) group (n = 7) and CP group (n = 7). Blood samples and fresh feces were collected at the end of the experimental period.RESULTS: The results displayed that supplementation with CP increased the concentrations of serum immunoglobulin A, immunoglobulin G, interleukin 6, and tumor necrosis factor-α (p < 0.05). However, there was no difference in the concentrations of serum amyloid A between the two groups (p > 0.05). Furthermore, the serum biochemical parameters of all the kittens were within the reference range. The relative abundance of beneficial bacteria (norank_f__Butyricicoccaceae and Bacteroides plebeius) was higher in the CP group (p < 0.05), while the opportunistic pathogen (Anaerotruncus) was lower in the CP group (p < 0.05). In addition, serum metabolomic analysis demonstrated that the differential metabolites, including arachidonic acid, dihomo-gamma-linolenic acid, and glycine, and the relevant metabolic pathway, including glyoxylate and dicarboxylate metabolism, glycine, serine, and threonine metabolism, and biosynthesis of unsaturated fatty acids, were implicated in regulating immune function in the kitten after CP treatment.CONCLUSION: CP supplementation can enhance immune function in kittens and increase the relative abundance of beneficial gut microbiota, and does not lead to generalized inflammation. Dietary supplementation with CP may generate nutritional benefits in kittens, and this study offers insight into the development of functional pet food for kittens.PMID:40109962 | PMC:PMC11920579 | DOI:10.3389/fmicb.2025.1500961

Food Chem X. 2025 Feb 25;26:102313. doi: 10.1016/j.fochx.2025.102313. eCollection 2025 Feb.ABSTRACTA novel two-step fermentation process was developed to enhance mead flavor quality. Headspace Solid-Phase Microextraction Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) with three columns was used to analyze the volatile profiles of meads, along with sensory evaluation and machine learning. Compared to traditional mead (TM), our novel mead (NM) reduced off-flavor compounds by 37.6 %, with isoamyl alcohol decreasing 1.26-fold and ethyl laurate 2.09-fold. Meanwhile, aromatic compounds increased by 39.41 %, with isoamyl acetate rising 3.31-fold, ethyl caproate 2.79-fold, and phenylethyl alcohol 1.69-fold. Sensory evaluation revealed a significant reduction in bitterness (41.1 %) and irritation (42.5 %), while fruity, sweet, and pleasantly sour flavors increased by 27.4 %, 36.9 %, and 45.5 % for NM. Key aroma compounds (benzaldehyde, 2,3-butanediol, cedrol) were identified via recombination and omission experiments. Dynamic monitoring and machine learning identified key rate-limiting steps, including the oxidation of benzeneacetaldehyde (phenylethyl alcohol synthesis), isovaleraldehyde (isoamyl alcohol synthesis), and the conversion of octanoic acid to decanoic acid.PMID:40109907 | PMC:PMC11919604 | DOI:10.1016/j.fochx.2025.102313

Front Med (Lausanne). 2025 Mar 5;12:1555077. doi: 10.3389/fmed.2025.1555077. eCollection 2025.ABSTRACTType 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by pathophysiological mechanisms such as insulin resistance and β-cell dysfunction. Recent advancements in T2DM research have unveiled intricate multi-level regulatory networks and contributing factors underlying this disease. The emergence of precision medicine has introduced new perspectives and methodologies for understanding T2DM pathophysiology. A recent study found that personalized treatment based on genetic, metabolic, and microbiome data can improve the management of T2DM by more than 30%. This perspective aims to summarize the progress in T2DM pathophysiological research from the past 5 years and to outline potential directions for future studies within the framework of precision medicine. T2DM develops through the interplay of factors such as gut microbiota, genetic and epigenetic modifications, metabolic processes, mitophagy, NK cell activity, and environmental influences. Future research should focus on understanding insulin resistance, β-cell dysfunction, interactions between gut microbiota and their metabolites, and the regulatory roles of miRNA and genes. By leveraging artificial intelligence and integrating data from genomics, epigenomics, metabolomics, and microbiomics, researchers can gain deeper insights into the pathophysiological mechanisms and heterogeneity of T2DM. Additionally, exploring the combined effects and interactions of these factors may pave the way for more effective prevention strategies and personalized treatments for T2DM.PMID:40109716 | PMC:PMC11919862 | DOI:10.3389/fmed.2025.1555077

Bladder Cancer. 2025 Mar 18;11(1):23523735251325100. doi: 10.1177/23523735251325100. eCollection 2025 Jan-Mar.ABSTRACTBACKGROUND: Metabolomic research and metabolomics-based biomarkers predicting treatment outcomes in bladder cancer remain limited.OBJECTIVE: We explored the serum metabolites potentially associated with the risk of recurrence after intravesical Bacillus Calmette-Guérin (BCG) therapy.METHODS: Two independent cohorts, a discovery cohort (n = 23) and a validation cohort (n = 40), were included in this study. Blood was collected before the induction of BCG therapy (pre-BCG blood; both discovery and validation cohorts) and after six doses of BCG (post-BCG blood; only discovery cohort). Metabolome analysis of serum samples was conducted using capillary electrophoresis time-of-flight mass spectrometry. The endpoint was intravesical recurrence-free survival, which was analysed using Kaplan-Meier estimates, the log-rank test, and the Cox proportional hazard model.RESULTS: Of the 353 metabolites quantified, nine (2.5%) and four (1.1%) were significantly upregulated and downregulated, respectively. The heatmap of hierarchical clustering analysis and principal coordinate analysis for the fold changes and in serum metabolites differentiated 10 recurrent cases and 13 non-recurrent cases in the discovery cohort. A metabolome response-based scoring model using 16 metabolites, including threonine and N6,N6,N6-trimethyl-lysine effectively stratified the risk of post-BCG recurrence. Additionally, pre-BCG metabolome-based score models using six metabolites, octanoylcarnitine, S-methylcysteine-S-oxide, theobromine, carnitine, indole-3-acetic acid, and valeric acid, were developed from the discovery cohort. Univariate and multivariate analyses confirmed a high predictive accuracy in the validation and combination cohorts.CONCLUSIONS: We demonstrated that numerous types of serum metabolites were altered in response to intravesical BCG and developed high-performance score models which might effectively differentiated the risk of post-BCG tumour recurrence.PMID:40109498 | PMC:PMC11921002 | DOI:10.1177/23523735251325100

Sichuan Da Xue Xue Bao Yi Xue Ban. 2025 Jan 20;56(1):68-73. doi: 10.12182/20250160110.ABSTRACTOBJECTIVE: To explore the mechanism by which Wandai Decoction prevents and treats vulvovaginal candidiasis (VVC) of the spleen deficiency and excessive dampness type and restores the vaginal flora structure, and to identify the potential metabolic pathways involved using metagenomics and metabolomics.METHODS: Twenty VVC patients who met the inclusion criteria were randomly assigned to a Wandai Decoction group and a fluconazole group (n = 10 in each group). Subjects in the fluconazole group were given a single oral dose of 150 mg fluconazole, while those in the Wandai Decoction group took the Wandai Decoction orally for 14 days. The vulvovaginal signs and symptoms (VSS) scores of both patient groups were evaluated before and after treatment. Vaginal secretions were collected before and after treatment. The Illumina sequencing and the liquid chromatography with tandem mass spectrometry (LC-MS/MS) platform were used to conduct metagenomic and metabolomics analyses of the vaginal secretions, respectively.RESULTS: The VSS score results showed that the VSS scores of both groups decreased after treatment compared with those before treatment (P < 0.01), and there was no statistically significant difference in the VSS scores between the two groups after treatment. Metagenomics results showed that, after treatment, the vaginal microbial communities in the Wandai Decoction group were of CST Ⅱ and Ⅴ types (predominated by Lactobacillus gasseri and Lactobacillus jensenii), while those in the fluconazole group were Lactobacillus_intestinalis and Streptococcus_sp._oral_ taxon_431. KEGG functional enrichment analysis results showed that, in terms of the cell cycle and meiosis functions of Candida albicans, statistically significant differences between the Wandai Decoction and fluconazole groups were observed (P < 0.05). Metabolomic analysis identified 120 differential metabolites between the two groups after treatment. The results of KEGG metabolic pathway enrichment analysis of differential metabolites showed that the Wandai Decoction might be significantly superior to fluconazole in improving local vaginal metabolic pathways of α-linolenic acid, glycerophospholipid metabolism, pentose and glucuronic acid interconversion, and arachidonic acid.CONCLUSION: The Wandai Decoction can improve the vaginal flora of VVC patients. It may be superior to fluconazole in the signaling pathways of the cell cycle and meiosis. The improvement of the vaginal flora by the Wandai Decoction may be associated with its effect on metabolic pathways of glycerophospholipid metabolism, pentose and glucuronic acid interconversion, and others in the vagina.PMID:40109467 | PMC:PMC11914014 | DOI:10.12182/20250160110

Sichuan Da Xue Xue Bao Yi Xue Ban. 2025 Jan 20;56(1):129-136. doi: 10.12182/20250160604.ABSTRACTOBJECTIVE: To investigate the regulatory effect of moxibustion, a traditional Chinese medicine therapy, on bone metabolism in ovariectomized (estrogen-deficient) mice and to explore its underlying mechanisms.METHODS: Female C57BL/6J mice of 12 weeks old were randomly assigned to five groups, including a sham operation control group (SHAM), an ovariectomy group (OVX), a group given ovariectomy and broad-spectrum antibiotics (OVX-A), a group given ovariectomy and moxibustion (OVX-M), and a group given ovariectomy, broad-spectrum antibiotics, and moxibustion (OVX-A-M), with 5 mice in each group. Then, 4 weeks post-surgery, the mice in each group received broad-spectrum antibiotics and/or moxibustion intervention for an additional 4 weeks. After that, the mice were sacrificed, and samples were collected. Micro-CT was used to assess bone volume parameters in the distal femurs, including bone volume/tissue fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and cortical thickness (Ct.Th). Targeted metabolomics was used to measure serum tryptophan metabolites, and qPCR was performed to quantify serotonin (SER) receptors Htr2a and Htr2b mRNA levels in bone marrow. In addition, primary bone marrow mesenchymal stem cells (BMSCs) were treated with serotonin of varying concentration gradients (0, 0.01, 0.1, 1, and 10 μmol/L). Alkaline phosphatase (ALP) staining was performed to assess osteogenic differentiation, while qPCR was performed to assess the expression of Colla1, an osteogenesis-related gene, and serotonin receptors Htr2a and Htr2b.RESULTS: Compared with the SHAM mice, the OVX mice exhibited significant deterioration in bone microarchitecture, showing decreased BV/TV ([10.57 ± 2.82]% vs. [4.20 ± 0.96]%, P < 0.01), reduced Tb.N ([3.16 ± 0.11] vs. [2.25 ± 0.15], P < 0.01), increased Tb.Sp ([0.31 ± 0.01] vs. [0.45 ± 0.03], P < 0.01), and decreased levels of serum tryptophan metabolite SER. Compared with the OVX mice, the OVX-M mice showed a notable improvement in bone microarchitecture, with BV/TV increasing to (7.51 ± 1.42)% (P < 0.05), and elevated levels of serum SER and bone marrow Htr2a gene expression (P < 0.05). However, the effect of moxibustion in reversing bone loss in OVX mice disappeared when the gut microbiota was disrupted by broad-spectrum antibiotics. OVX-A-M mice had significantly lower serum serotonin levels compared to OVX-M mice (P < 0.001). According to the findings from the in vitro experiments, SER enhanced the osteogenic differentiation of BMSCs, with the optimal effect achieved at a concentration of 0.1 μmol/L. Furthermore, SER at 0.1 μmol/L significantly increased the expression levels of osteogenesis-related genes Colla1 and Htr2a (P < 0.05).CONCLUSION: Moxibustion therapy can inhibit postmenopausal bone loss, potentially by regulating gut microbiota-derived SER, activating the 5-HT2A receptor, and promoting the osteogenic differentiation of BMSCs.PMID:40109464 | PMC:PMC11914029 | DOI:10.12182/20250160604

NAR Genom Bioinform. 2025 Mar 19;7(1):lqaf022. doi: 10.1093/nargab/lqaf022. eCollection 2025 Mar.ABSTRACTThe yeast metabolic cycle (YMC), characterized by cyclic oscillations in transcripts and metabolites, is an ideal model for studying biological rhythms. Although multiple omics datasets on the YMC are available, a unified landscape for this process is missing. To address this gap, we integrated multi-omics datasets by singular value decompositions (SVDs), which stratify each dataset into two levels and define four eigen-phases: primary 1A/1B and secondary 2A/2B. The eigen-phases occur cyclically in the order 1B, 2A, 1A, and 2B, demonstrating an interplay of induction and repression: one eigen-phase induces the next one at a different level, while represses the other one at the same level. Distinct molecular characteristics were identified for each eigen-phase. Novel ones include the production and consumption of glycerol in eigen-phases 2A/2B, and the opposite regulation of ribosome biogenesis and aerobic respiration between 2A/2B. Moreover, we estimated the timing of multi-omics: histone modifications H3K9ac/H3K18ac precede mRNA transcription in ∼3 min, followed by metabolomic changes in ∼13 min. The transition to the next eigen-phase occurs roughly 38 min later. From epigenome H3K9ac/H3K18ac to metabolome, the eigen-entropy increases. This work provides a computational framework applicable to multi-omics data integration.PMID:40109351 | PMC:PMC11920873 | DOI:10.1093/nargab/lqaf022

Cell Prolif. 2025 Mar 20:e70024. doi: 10.1111/cpr.70024. Online ahead of print.ABSTRACTDiminished ovarian reserve (DOR) is a pathological condition characterised by reduced ovarian function, which refers to the decreased quality and quantity of oocytes, potentially causing female infertility and various health issues. Follicular fluid (FF) serves as the microenvironment for follicular development and oocyte maturation, gaining an in-depth understanding of the metabolic state of FF will help us uncover the key biological processes involved in ovarian aging, while the specific underlying pathogenic mechanisms are not fully understood. In this study, we utilised pseudotargeted metabolomic analysis of FF to reveal the glycerophospholipid metabolism dysfunction mediated by GPD1L in DOR patients. We also found that GPD1L was downregulated in granulosa cells (GCs) of DOR patients, resulting in increased cell apoptosis and mitochondrial dysfunction. Moreover, our results demonstrated that the downregulated expression of GPD1L could induce follicular atresia and impair oocyte quality in mouse ovaries. Altogether, our research suggested that GPD1L in GCs and the key metabolites in the glycerophospholipid metabolism pathway could potentially act as novel biomarkers of DOR diagnosis, paving the way for a new theoretical basis for understanding the pathogenesis of DOR.PMID:40108995 | DOI:10.1111/cpr.70024

J Sep Sci. 2025 Mar;48(3):e70119. doi: 10.1002/jssc.70119.ABSTRACTCapillary electrochromatography (CEC) has attracted significant attention and gained considerable recognition in the field of separation science owing to its excellent separation efficiency. While numerous reviews on CEC have been published in recent years, a comprehensive and systematic summary of the typical synthesis strategies for electrochromatographic stationary phases and their state-of-the-art applications in CEC remains lacking. This review highlights recent advances (over the past 3 years) and representative applications (including chiral separation, microextraction-coupled analysis, metabolomics, enzyme analysis, and food analysis) of monolithic and open-tubular stationary phases in CEC. The advantages and limitations of each methodology are critically analyzed to present a balanced evaluation. Additionally, this work outlines future prospects regarding the development trends in electrochromatographic stationary phase preparation methods and the evolving applications of CEC.PMID:40108917 | DOI:10.1002/jssc.70119

J Proteome Res. 2025 Mar 19. doi: 10.1021/acs.jproteome.5c00010. Online ahead of print.ABSTRACTBACKGROUND: Colorectal carcinoma (CRC) is a leading cause of cancer-related deaths globally. Diagnostic biomarkers are essential for risk stratification and early detection, potentially enhancing patient survival. Our study aimed to explore the potential biomarkers of CRC at the protein and metabolic levels.METHODS: Blood serum from CRC patients and healthy controls was analyzed using metabolomic and proteomic techniques. A conjoint analysis was conducted, and samples were split into training and validation sets (7:3 ratio) to develop and evaluate a disease diagnosis classifier model. Immunohistochemistry (IHC) analyses were conducted to validate the results.RESULTS: We identified 631 differential metabolites and 61 differentially expressed proteins (DEPs) in CRC, involved in pathways such as arginine and proline metabolism, central carbon metabolism in cancer, and signaling pathways including TGF-β, mTOR, PI3K-Akt, and others. Key proteins (CILP2, SLC3A2, EXTL2, hydroxypyruvate isomerase (HYI), ENPEP, LRG1, CTSS, thyrotropin-releasing hormone-degrading ectoenzyme (TRHDE), SELE, and HSPA1A) showed significant expression differences between CRC patients and controls. IHC results showed that compared with the paracancerous tissues, the expression of CILP2, EXTL2, and HYI was significantly downregulated in the CRC tissues (P < 0.05). The classifier model, comprising l-arginine, Harden-Young ester, l-aspartic acid, oxoglutaric acid, l-proline, octopine, l-valine, and progesterone, achieved AUC values of 0.998 and 0.914 in training and validation data sets, respectively.CONCLUSIONS: The identified metabolites and DEPs are promising CRC biomarkers. The developed classifier model based on eight metabolites demonstrates high accuracy for CRC assessment and diagnosis.PMID:40108892 | DOI:10.1021/acs.jproteome.5c00010

Environ Microbiol. 2025 Mar;27(3):e70064. doi: 10.1111/1462-2920.70064.ABSTRACTDissolved organic matter (DOM) comprises diverse compounds with variable bioavailability across aquatic ecosystems. The sources and quantities of DOM can influence microbial growth and community structure with effects on biogeochemical processes. To investigate the chemodiversity of labile DOM in tropical reef waters, we tracked microbial utilisation of over 3000 untargeted mass spectrometry ion features exuded from two coral and three algal species. Roughly half of these features clustered into over 500 biologically labile spectral subnetworks annotated to diverse structural superclasses, including benzenoids, lipids, organic acids, heterocyclics and phenylpropanoids, comprising on average one-third of the ion richness and abundance within each chemical class. Distinct subsets of these labile compounds were exuded by algae and corals during the day and night, driving differential microbial growth and substrate utilisation. This study expands the chemical diversity of labile marine DOM with implications for carbon cycling in coastal environments.PMID:40108841 | DOI:10.1111/1462-2920.70064

Chin Med J (Engl). 2025 Mar 19. doi: 10.1097/CM9.0000000000003510. Online ahead of print.NO ABSTRACTPMID:40108783 | DOI:10.1097/CM9.0000000000003510

Plant Cell Environ. 2025 Mar 19. doi: 10.1111/pce.15456. Online ahead of print.ABSTRACTBacteriophages impact soil bacteria through lysis, altering the availability of organic carbon and plant nutrients. However, the magnitude of nutrient uptake by plants from lysed bacteria remains unknown, partly because this process is challenging to investigate in the field. In this study, we extend ecosystem fabrication (EcoFAB 2.0) approaches to study plant-bacteria-phage interactions by comparing the impact of virocell (phage-lysed) and uninfected 15N-labelled bacterial necromass on plant nitrogen acquisition and rhizosphere exometabolites composition. We show that grass Brachypodium distachyon derives some nitrogen from amino acids in uninfected Pseudomonas putida necromass lysed by sonication but not from virocell necromass. Additionally, the bacterial necromass elicits the formation of rhizosphere exometabolites, some of which (guanosine), alongside tested aromatic acids (p-coumaric and benzoic acid), show bacterium-specific effects on bacteriophage-induced lysis when tested in vitro. The study highlights the dynamic feedback between virocell necromass and plants and suggests that root exudate metabolites can impact bacteriophage infection dynamics.PMID:40108761 | DOI:10.1111/pce.15456

Microbiome. 2025 Mar 19;13(1):78. doi: 10.1186/s40168-025-02070-5.ABSTRACTBACKGROUND: The gut microbiome functions as a metabolic organ, producing numerous enzymes that influence host health; however, their substrates and metabolites remain largely unknown.RESULTS: We present MicrobeRX, an enzyme-based metabolite prediction tool that employs 5487 human reactions and 4030 unique microbial reactions from 6286 genome-scale models, as well as 3650 drug metabolic reactions from the DrugBank database (v.5.1.12). MicrobeRX includes additional analysis modules for metabolite visualization and enzymatic and taxonomic analyses. When we applied MicrobeRX to 1083 orally administered drugs that have been approved in at least one jurisdiction at some point in time (DrugBank), it predicted metabolites with physicochemical properties and structures similar to metabolites found in biosamples (from MiMeDB). It also outperformed another existing metabolite prediction tool (BioTransformer 3.0) in terms of predictive potential, molecular diversity, reduction of redundant predictions, and enzyme annotation.CONCLUSIONS: Our analysis revealed both unique and overlapping metabolic capabilities in human and microbial metabolism and chemo- and taxa-specific microbial biotransformations. MicrobeRX bridges the genomic and chemical spaces of the gut microbiome, making it a valuable tool for unlocking the chemical potential of the gut microbiome in human health, the food and pharmaceutical industries, and environmental safety. Video Abstract.PMID:40108657 | DOI:10.1186/s40168-025-02070-5

Commun Biol. 2025 Mar 19;8(1):459. doi: 10.1038/s42003-025-07911-5.ABSTRACTAntimicrobial resistance poses a severe threat to human health, with colistin serving as a critical medication in clinical trials against multidrug-resistant Gram-negative bacteria. However, the efficacy of colistin is increasingly compromised due to the rise of MCR-positive bacteria worldwide. Here, we reveal a notable metabolic disparity between mcr-positive and -negative bacteria through transcriptome and metabolomics analysis. Specifically, pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, was significantly diminished in mcr-positive bacteria. Conversely, supplementing with PLP could reverse the metabolic profile of drug-resistant bacteria and effectively restore colistin's bactericidal properties. Mechanistically, PLP was found to augment bacterial proton motive force by inhibiting the Kdp transport system, a bacterial K+ transport ATPase, thereby facilitating the binding of the positively charged colistin to the negatively charged bacterial membrane components. Furthermore, PLP supplementation triggers ferroptosis-like death by accumulating ferrous ions and inducing lipid peroxidation. These two modes of action collectively resensitize mcr-harboring Gram-negative bacteria to colistin therapy. Altogether, our study provides a novel metabolic-driven antibiotic sensitization strategy to tackle antibiotic resistance and identifies a potentially safe antibiotic synergist.PMID:40108411 | DOI:10.1038/s42003-025-07911-5

Sci Rep. 2025 Mar 19;15(1):9437. doi: 10.1038/s41598-025-94018-w.ABSTRACTWilliams-Beuren syndrome (WBS, OMIM-no.194050) is a rare congenital genetic disorder primarily marked by developmental delays and cardiovascular anomalies, with potential involvement of metabolic dysregulation. Despite this, the metabolic features of WBS have not been extensively studied. Thus, our objective was to examine the serum metabolome profile in children with WBS, elucidating metabolic changes and associated pathways in the disorder. We recruited 25 children with WBS (mean age 5.0 ± 2.6 years, 40% female) from the Children's Hospital affiliated to Zhejiang University between 2020 and 2023. An age and sex matched healthy control group (N = 25) were recruited from the Health Management Center in the same hospital. Clinical information of WBS were extracted from the medical records. Blood samples were obtained for untargeted metabolomics analysis using UPLC-MS/MS. The metabolomic profiles of WBS patients were compared to those of healthy controls to identify metabolites with differential abundance. Enrichment analysis was conducted to identify potentially impacted KEGG pathways. Associations between metabolites and phenotypes were evaluated. Children with WBS exhibited a unique metabolic profile compared to healthy controls, as evidenced by the identification of 465 untargeted metabolites in serum. Of these metabolites, 169 showed differential abundance in WBS children. The top enriched KEGG pathways in WBS children included nicotine addiction, cholesterol metabolism, arginine biosynthesis, retrograde endocannabinoid signaling. Additionally, there were indications of potential metabolic alterations in the L-tryptophan pathway, with a shift from serotonin to L-kynurenine, as well as disruptions in bile acid metabolism. Metabolome data in children with WBS showed neurological and amino acid metabolism changes, indicating multisystem involvement and developmental delay. This data can help monitor and manage the disease, but further studies are needed to understand the underlying mechanisms and consequences.PMID:40108238 | DOI:10.1038/s41598-025-94018-w

NPJ Sci Food. 2025 Mar 19;9(1):33. doi: 10.1038/s41538-025-00398-8.ABSTRACTStenophylla coffee, an undomesticated species from Upper West Africa, is of commercial interest due to its high heat tolerance and Arabica-like flavour. To investigate the chemical basis of flavour similarity, we analysed unroasted coffee bean samples using liquid chromatography-mass spectrometry (LC-MS) and applied metabolomics approaches to compare chemical profiles. We report similarities between Arabica and stenophylla in the relative levels of several key compounds linked to coffee flavour, including caffeine, trigonelline, sucrose and citric acid. Differences in their chemical profiles were also observed, especially in their diterpenoid and hydroxycinnamic acid profiles. We report the additional novel finding that theacrine occurs in stenophylla, which is the first record of this alkaloid in coffee beans. For stenophylla, the dissimilarities in chemical compound composition (compared to Arabica) may offer opportunities for a better understanding of the chemical basis of high-quality coffee and sensory diversification.PMID:40108189 | DOI:10.1038/s41538-025-00398-8