PubMed
Prediabetes and type 2 diabetes but not obesity are associated with alterations in bile acid related gut microbe-microbe and gut microbe-host community metabolism
Gut Microbes. 2025 Dec;17(1):2474143. doi: 10.1080/19490976.2025.2474143. Epub 2025 Mar 5.ABSTRACTThe interplay between bile acids (BAs) and metabolic diseases has gained importance in recent years, with a variety of studies investigating their relationship with diverging results. Therefore, in the present study we performed a detailed analysis of BA metabolism in 492 subjects with different metabolic phenotypes. Besides microbiomics and metabolomics this investigation included in silico analysis of community metabolism to examine metabolic interchange between different microbes as well as microbes and the human host. Our findings revealed distinct changes in the BA profiles of patients with diabetes and prediabetes, whereas obesity alone had no influence on circulating BAs. Impaired glycemic control led to increased circulating BAs, a shift toward more secondary BAs, and an increase in the ratio of glycine to taurine-conjugated BAs. Additional analyses revealed that the ratio of glycine to taurine conjugation demonstrated variations between the single BAs, cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), regardless of the metabolic status, with CA having a higher fraction of taurine conjugation. Furthermore, we found that microbiome alterations are associated with BAs, independent of diabetes or obesity. Analysis of microbial community metabolism revealed differential relative pathway abundance in relation to diabetes, particularly those related to membrane and polyamine synthesis. Increased bacterial cross-feeding of polyamines, galactose, and D-arabinose also coincided with an increase in BA. Notably, our serum metabolome analysis mirrored several of the previously in silico predicted exchanged metabolites, especially amino acid metabolism. Therefore, targeting BA metabolism may be a future approach for the treatment of metabolic diseases, especially prediabetes and type 2 diabetes.PMID:40045464 | DOI:10.1080/19490976.2025.2474143
Spermine accumulation via spermine synthase promotes tumor cell proliferation in head and neck squamous cell carcinoma
BMC Cancer. 2025 Mar 5;25(1):402. doi: 10.1186/s12885-025-13820-x.ABSTRACTBACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is among the most aggressive malignancies, underscoring the need for early diagnosis to improve patient outcomes. Tumor-derived exosomes, which can be non-invasively obtained and reflect the metabolic state of tumors in real-time, are under increasing investigation for their diagnostic potential. Herein we analyzed metabolite differences in exosomes, serum, and tissues from patients with HNSCC to identify potential diagnostic biomarkers of clinical relevance.METHODS: Non-targeted metabolomics based on liquid chromatography-mass spectrometry was employed to quantify metabolites in exosome, serum, and tissue samples from 11 patients with HNSCC and six patients without cancer. The metabolic profiles of HNSCC were analyzed through univariate and multivariate statistical methods, differential metabolite analysis, and pathway enrichment analysis.RESULTS: We identified three differential metabolites in exosomes, 45 in serum, and 33 in tissues. Notably, patients with HNSCC exhibited significant disruptions in protein and amino acid metabolism. Spermine was exclusively detected in exosomes and tissues from patients with HNSCC. We hypothesize that spermine is extracellularly secreted by malignant cells via exosomes and subsequently enters the bloodstream. Moreover, spermine synthase was highly expressed in HNSCC tissues. Knocking down spermine synthase markedly impaired HNSCC cell proliferation and migration.CONCLUSIONS: This study provides a preliminarily characterization of the metabolic profile of HNSCC and highlights spermine and its synthetic pathways as potential diagnostic and therapeutic targets. Future studies are warranted to elucidate the mechanism of action of spermine in HNSCC and explore its utility in early diagnosis and therapeutic development.PMID:40045286 | DOI:10.1186/s12885-025-13820-x
Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations
Nat Metab. 2025 Mar 5. doi: 10.1038/s42255-025-01245-6. Online ahead of print.ABSTRACTPreclinical studies have shown that asparagine deprivation enhances T cell antitumour responses. Here we apply compassionate use of L-asparaginase, usually employed to treat blood malignancies, on patients with recurrent metastatic nasopharyngeal carcinoma. The use of L-asparaginase notably enhances immune-checkpoint blockade therapy in patients by strengthening CD8+T cell fitness. Our study shows that this combination is a promising avenue for clinical application and provides further mechanistic insight into how asparagine restriction rewires T cell metabolism.PMID:40045118 | DOI:10.1038/s42255-025-01245-6
Omics advancements towards exploring arsenic toxicity and tolerance in plants: a review
Planta. 2025 Mar 5;261(4):79. doi: 10.1007/s00425-025-04646-9.ABSTRACTOmics approaches provide comprehensive insights into plant arsenic stress responses, setting the stage for engineering arsenic-tolerant crops. Understanding arsenic (As) toxicity in plants is crucial for environmental and agricultural sustainability, considering the implications of As in impacting soil productivity and environmental health. Although some articles already examined the detailed molecular mechanisms behind As toxicity and tolerance, a comprehensive review of recent omics advancements in studying plant responses to As exposure is needed. The present review highlights the valuable contribution of omics approaches (genomics, transcriptomics, proteomics, and metabolomics) to characterize the intricate response to As overall, which could empower As-tolerant plant development. Genomic techniques, such as QTL mapping, GWAS, RAPD, and SSH, hold the potential to provide valuable insights into the genetic diversity and expression patterns associated with the plant response to As stress, highlighting also the power of new advanced technology such as CRISPR-Cas9. Transcriptomics approaches (e.g., microarrays and RNA sequencing) revealed gene expression patterns in plants under As stress, emphasizing the role of sulfur metabolism in As tolerance. Proteomics, using 2-DE combined with MALDI-ToF MS or ESI-MS/MS, offers insights into the stress-inducible proteins and their involvement in As toxicity mitigation, while iTRAQ-based proteomics enabled an understanding of cultivar-specific responses under high As concentration. Metabolomics, with LC-MS, GC-MS, (U)HPLC, and NMR, elucidated small molecule alterations and complex metabolic activities occurring under As plant exposure. Compendium of data and evidence-related tools offers a foundation for advancing As-tolerant plant development and promoting environmental and agricultural resilience.PMID:40044842 | DOI:10.1007/s00425-025-04646-9
Transcriptome and metabolite conjoint analysis reveals the seed dormancy release process of perilla
Sci Rep. 2025 Mar 5;15(1):7763. doi: 10.1038/s41598-025-91039-3.ABSTRACTSeed dormancy is a common physiological phenomenon during storage which has a great impact on timely germination of seeds. An in-depth analysis of the physiological and molecular mechanisms of perilla seed dormancy release is of great significance for cultivating high-vigor perilla varieties. We used gibberellin A3-soaked seeds (GA), natural dormancy-release seeds (CK) and water-soaked seeds (WA) to study the changes in the transcriptome and metabolome of dormancy release. The germination test revealed that the optimum concentration of gibberellin A3 for releasing dormancy from perilla seeds was 200 mg/L. The results revealed that plant hormone signal transduction, starch and sucrose metabolism and citric acid cycle were significantly enriched metabolic pathways closely related to seed dormancy release. Perilla seeds release their dormancy by enhancing the expression of GID1, PIF3, SnRK2, IAA, ARR-A, GH3, MKK4_5, otsB, GN1_2_3, glgC, WAXY, inhibiting the expression of DELLA, PP2C, glga, bglX, and GN4, and regulating the content of gibberellin A4, abscisic acid, auxin, sucrose, maltose, trehalose, and α-D-glucose 1-phosphate. Auxin plays an important role in breaking perilla seed dormancy and promoting seed germination. The energy required for breaking seed dormancy and germination of perilla seeds is mainly provided through sucrose metabolism. Citric acid cycle (TCA cycle) is the main energy supply transformation pathway for seed germination.PMID:40044827 | DOI:10.1038/s41598-025-91039-3
Author Correction: Spatiotemporal transcriptome and metabolome landscapes of cotton somatic embryos
Nat Commun. 2025 Mar 5;16(1):2213. doi: 10.1038/s41467-025-57675-z.NO ABSTRACTPMID:40044695 | DOI:10.1038/s41467-025-57675-z
Author Correction: Spatiotemporal transcriptome and metabolome landscapes of cotton fiber during initiation and early development
Nat Commun. 2025 Mar 5;16(1):2215. doi: 10.1038/s41467-025-57674-0.NO ABSTRACTPMID:40044665 | DOI:10.1038/s41467-025-57674-0
Multi-Omics Reveal the Metabolic Changes in Cumulus Cells During Aging
Cell Prolif. 2025 Mar 5:e70014. doi: 10.1111/cpr.70014. Online ahead of print.ABSTRACTMaternal age has been reported to impair oocyte quality. However, the molecular mechanisms underlying the age-related decrease in oocyte competence remain poorly understood. Cumulus cells establish direct contact with the oocyte through gap junctions, facilitating the provision of crucial nutrients necessary for oocyte development. In this study, we obtained the proteomic and metabolomic profiles of cumulus cells from both young and old mice. We found that fatty acid beta-oxidation and nucleotide metabolism, markedly active in aged cumulus cells, may serve as a compensatory mechanism for energy provision. Tryptophan undergoes two principal metabolic pathways, including the serotonin (5-HT) synthesis and kynurenine catabolism. Notably, we discovered that kynurenine catabolism is reduced in aged cumulus cells compared to young cells, whereas 5-HT synthesis exhibited a significant decrease. Furthermore, the supplement of 5-HT during cumulus-oocyte complexes (COCs) culture significantly ameliorated the metabolic dysfunction and meiotic defects in old oocytes. In sum, our data provide a comprehensive multiple omics resource, offering potential insights for improving oocyte quality and promoting fertility in aged females.PMID:40044606 | DOI:10.1111/cpr.70014
Bootstrap inference and machine learning reveal core differential plasma metabolic connectome signatures in major depressive disorder
J Affect Disord. 2025 Mar 3:S0165-0327(25)00325-8. doi: 10.1016/j.jad.2025.02.109. Online ahead of print.ABSTRACTBACKGROUND: Major depressive disorder (MDD) involves molecular alterations and pathway dysregulation. Metabolic interconnections are crucial for normal functioning, yet current analysis focuses on individual pathways or biomarkers, overlooking intricate metabolic biomarker interactions.METHODS: Plasma metabolomic data from 182,053 UK Biobank participants [9425 MDD, and 172,628 healthy controls (HC)] were used to construct metabolic correlation networks through bootstrap inference analysis (bootstrap step size: 1000, 3000, 5000, 7000, 9000; n = 1000 times/size). Differential core metabolic network signatures between MDD and HC were identified by machine learning, followed by metabolic pathway analysis. Various deep learning and machine learning models were employed to differentiate MDD from HC groups using the identified network features and baseline characteristics.RESULTS: The MDD metabolic network showed marked reorganization, with a sparser and more streamlined network structure compared to controls (p < 0.05 for both Vnet-edge and Vnet-node). Analysis of the core network in MDD revealed four key altered pathways, with linoleic acid metabolism being the most influential (p < 0.01, impact = 0.29). An extreme gradient boosting model combining network signatures and baseline features achieved 73 % accuracy, and an AUROC of 0.82 in differentiating MDD from HC groups.CONCLUSIONS: This large-scale, metabolomic connectome analysis revealed consistent dysregulated metabolic network features in MDD, providing a robust and distinguishable framework compared to controls. The MDD network exhibits distinct connectivity patterns, particularly within linoleic acid metabolism. Integrating metabolomics as networks, rather than isolated markers, offers a promising approach for elucidating MDD pathophysiology and identifying diagnostic biomarkers.PMID:40044084 | DOI:10.1016/j.jad.2025.02.109
The oleaginous yeast Rhodosporidium toruloides engineered for biomass hydrolysate-derived (E)-⍺-bisabolene production
Metab Eng. 2025 Mar 3:S1096-7176(25)00030-8. doi: 10.1016/j.ymben.2025.02.014. Online ahead of print.ABSTRACTThe oleaginous yeast R. toruloides has been exploited for many bioproducts, including several terpenes, owing to its oleaginous nature and biomass inhibitor tolerance. Here, we built upon previous (E)-⍺-bisabolene work by iteratively stacking the complete mevalonate pathway from Saccharomyces cerevisiae onto a multicopy bisabolene synthase parent strain. Metabolomics and proteomics verified heterologous pathway expression and identified metabolic bottlenecks at three intermediate steps, with candidate feedback-resistant mevalonate kinases screening improving titers 15%. Subtle differences in codon optimization, and preliminary attenuation of completing flux toward lipids resulted in 6-fold, 7-fold higher titers relative to controls, respectively. Media optimization led to modest improvements, with zinc identified as the most promising at 10% titer improvement. Ultimately, high-performance strains were cultivated with corn-stover biomass hydrolysate in microtiter plates at 300 g/L total sugar, achieving 20.8 g/L bisabolene, the highest reported titer in the literature. A 2 L glucose minimal medium bioreactor achieved 19.3 g/L bisabolene and a literature-high productivity of 0.11 g/L/h.PMID:40044027 | DOI:10.1016/j.ymben.2025.02.014
Radix Hedysari Polysaccharides modulate the gut-brain axis and improve cognitive impairment in SAMP8 mice
Int J Biol Macromol. 2025 Mar 3:141715. doi: 10.1016/j.ijbiomac.2025.141715. Online ahead of print.ABSTRACTOBJECTIVE: Radix Hedysari Polysaccharides (RHP) are the principal bioactive constituents of the traditional Chinese medicinal herb Radix Hedysari. This study aims to evaluate the neuroprotective effects of RHP in both cellular and animal models of Alzheimer's disease (AD) and to elucidate the underlying molecular mechanisms.METHODS: HT22 cells subjected to Aβ25-35-induced cytotoxicity were pretreated with RHP, followed by assessments of reactive oxygen species (ROS) generation, mitochondrial superoxide (mSOX) levels, and mitochondrial membrane potential (ΔΨm). Senescence-accelerated mouse-prone 8 (SAMP8) mice were orally administered RHP for 12 weeks. Behavioral assays were conducted to assess cognitive function, while metabolomic and proteomic analyses were performed to examine serum metabolic alterations and hippocampal protein expression profiles. Additionally, neuronal autophagy and gut barrier integrity were evaluated using immunohistochemistry, transmission electron microscopy, and biomarker quantification.RESULTS: RHP treatment significantly attenuated Aβ25-35-induced oxidative stress in HT22 cells by reducing ROS and mSOX production while preserving ΔΨm. In SAMP8 mice, RHP improved cognitive performance, preserved hippocampal mitochondrial ultrastructure, and enhanced neuronal autophagic activity. Moreover, RHP modulated serum metabolic pathways and alleviated gut barrier dysfunction, suggesting a role in gut-brain axis regulation.CONCLUSION: RHP ameliorates cognitive impairment in SAMP8 mice, potentially through its modulation of systemic metabolism, mitigation of neuronal mitochondrial damage, and restoration of gut barrier integrity. These findings highlight the therapeutic potential of RHP in AD intervention and warrant further investigation into its mechanistic underpinnings.PMID:40044002 | DOI:10.1016/j.ijbiomac.2025.141715
Widely targeted metabolomics to analyze the effect of polyvinyl alcohol/pullulan/ZnO-Nps composite film on postharvest storage of Allium mongolicum regel
Int J Biol Macromol. 2025 Mar 3:141667. doi: 10.1016/j.ijbiomac.2025.141667. Online ahead of print.ABSTRACTIn this study, a composite film (CF) made of polyvinyl alcohol, pullulan, and ZnO nanoparticles was prepared by solution casting. The CF were applied to the postharvest preservation of Allium mongolicum Regel. Widely targeted metabolomics analysis of A. mongolicum Regel by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to investigate the mechanism of action of active substances in A. mongolicum Regel during CF-treated storage process. Analysis of the results showed that 1534 metabolites were present in CF-treated A. mongolicum Regel, of which 175 metabolites were significantly different. KEGG analysis showed that the differential metabolites were mainly involved in metabolic pathways, secondary metabolite biosynthesis, including the biosynthetic metabolism of compounds such as flavonoids and phenolic acids and alkaloids. The changes in these secondary metabolites further affected key metabolic pathways such as flavonoid biosynthesis, phenylalanine metabolism, carbon fixation in photosynthesis and glycolysis. These results help to explain the preservation mechanism of A. mongolicum Regel during the storage period and provide an important theoretical basis for the preservation of A. mongolicum Regel composite film packaging in the future.PMID:40043986 | DOI:10.1016/j.ijbiomac.2025.141667
In vitro fermentation of Auricularia auricula polysaccharides and their regulation of human gut microbiota and metabolism
Int J Biol Macromol. 2025 Mar 3:141714. doi: 10.1016/j.ijbiomac.2025.141714. Online ahead of print.ABSTRACTAuricularia auricula is abundant in polysaccharides that received increasing attention due to their variety biological activities and prebiotic potential. In order to explore the role of A. auricula polysaccharides (AAP) in regulating human gut microbiota and metabolic health, this study employed metagenomic and metabolomic analyses to examine the impact of AAP on the gut microbiota via in vitro fecal fermentation experiments. After in vitro fermentation, the data indicated that gut microbiota utilized AAP to produce rich short-chain fatty acids (SCFAs) including acetic acid, propionic acid, butyric acid and modulate gut microbiota structure, such as increasing the proportion of Bacteroidetes to Firmicutes, elevating the abundance of beneficial bacteria, including Bacteroides, especially the Parabacteroides, and inhibiting the abundance of harmful bacteria such as Bilophila, Morganella, and Escherichia-Shigella. Furthermore, the metabolomic analysis indicated that AAP utilization by gut microbes substantially alters the metabolic profile, in which 26 potential biological biomarkers were found and affects tryptophan, bile acids, purines, and butyric acid pathways to promote host health. In conclusion, this research indicated that AAP has a prebiotic potential, which can regulate the gut microbiota and promote host health. Moreover, this study provided scientific evidence for using AAP as a functional food with prebiotic effect.PMID:40043973 | DOI:10.1016/j.ijbiomac.2025.141714
Ecosurveillance reveals subtle metabolic effects on the non-native cane toad (Rhinella marina) from low levels of accumulated environmental per- and polyfluoroalkyl substances
Environ Pollut. 2025 Mar 3:125968. doi: 10.1016/j.envpol.2025.125968. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment, bioaccumulate, and may have toxic effects. This study used non-native cane toads (Rhinella marina) to examine PFAS and metal accumulation and impacts in large terrestrial amphibians from urban and peri-urban areas. We quantified 38 PFAS compounds and 36 environmental and legacy metal(loid)s in 52 adult cane toad livers collected from six locations around Southeast Queensland, Australia, along a known PFAS gradient. Associations among PFAS, metal(loid) concentrations, and whole-organism metrics were assessed. An omics-led approach assessed biochemical responses in liver, muscle, fat and gonad/egg tissues associated with these PFAS concentrations. Liver PFAS concentrations ranged from 0.5 to 82.1 μg/kg ww, with one male outlier at 452 μg/kg ww (mean: 18 ± 21 SD μg/kg ww, excluding outlier). PFOS was the most dominant PFAS (60 ± 26 SD% of total), followed by PFDoDA (13 ± 9 SD%). The liver metal(loid)s with statistically significant variation among locations and sex were Al, As, Ca, Cu, Mn, Ni, Se, Sn, Sr and V. Total PFAS had no associations with whole-organism metrics, and body condition and relative femur length showed a weak interaction effect between PFAS and Ni. Metabolic profiling revealed sex-specific differences linked to total PFAS, with females showing a broader metabolic perturbation. The strongest metabolic signals were in glycerolipid metabolism, ether lipid metabolism, and fatty acid biosynthesis, though these effects were statistically weak. PFAS and metal(loid) levels were low compared to those previously recorded in tertiary consumers and aquatic vertebrates from contaminated areas. Despite minor metabolomic changes, the overall health impact was minimal. These findings contribute to the development of tissue PFAS guideline values for wild amphibians, but further studies on higher PFAS levels of accumulation and responses of additional amphibian species are needed.PMID:40043876 | DOI:10.1016/j.envpol.2025.125968
Long-term and low-dose exposure to triclosan induces POI phenotype in female offspring mice
Environ Pollut. 2025 Mar 3:125966. doi: 10.1016/j.envpol.2025.125966. Online ahead of print.ABSTRACTTriclosan (TCS), a typical endocrine disruptor, is widely used as an antibacterial agent in consumer goods. However, there are few studies on the effects of long-term low-dose TCS exposure on ovarian function in F1 female mice. In this paper, F1 female mice were exposed to TCS (0-3000 μg/kg/day) from intrauterine to postnatal day (PND) 91 to investigate its effects on the ovary. The results revealed that the number of total follicles was decreased, while atretic follicles was increased after TCS exposure. At the hormonal level, the secretion of estradiol was reduced, while follicle-stimulating hormone and luteinizing hormone were increased after TCS exposure. Observation of vaginal smear showed that TCS disrupted the estrous cycle of F1 female mice, especially at the dose of 3000 μg/kg/day. Moreover, TCS promoted cell apoptosis by activating the p38-MAPK signaling pathway and oxidative stress in vitro. In addition, analysis of the fecal microbiome and serum metabolomics revealed that exposure to TCS may cause gut microbiota disruption and metabolic abnormalities in F1 female mice. In conclusion, long-term low-dose TCS exposure may induce primary ovarian insufficiency phenotype in F1 female mice via inducing cell apoptosis and disrupting gut microbiota and metabolism.PMID:40043874 | DOI:10.1016/j.envpol.2025.125966
Longitudinal characterization of the metabolome of dairy cows transitioning from one lactation to the next: Investigations in fecal samples
J Dairy Sci. 2025 Mar 3:S0022-0302(25)00132-8. doi: 10.3168/jds.2025-26273. Online ahead of print.ABSTRACTThe fecal metabolome comprises metabolites that are excreted or not absorbed by the animal. This study examined the changes in the fecal metabolome of dairy cows from the end of one lactation period, through the dry period, and into the subsequent lactation. Twelve Holstein cows (BW = 745 ± 71 kg, BCS = 3.43 ± 0.66) were housed in a tie-stall barn from 7 wk before to 15 wk after parturition, with dry-off occurring approximately 6 wk before the expected calving date (mean dry-off time = 42 d). Fecal samples were taken at wk -7, -5, -1, +1, +5, +10, +15 relative to calving. Targeted metabolomics identified a total of 93 metabolites, including AA, biogenic amines, bile acids (BA), and acylcarnitines (AcylCN) and some phospholipids. Principal component analysis (PCA) revealed clear metabolic shifts that showed a clear separation between the samples from the dry period and the samples from the end, early and middle of lactation, indicating significant changes in the metabolic profiles in the feces. The transition from the dry period (wk -5, -1 relative to calving) to lactation (wk +1, +5, +10, +15, -7 relative to calving) is characterized by an increase in fecal AA and metabolites, such as Glu, Met, β-alanine, and methionine sulfoxide, reflecting a shift in nitrogen metabolism to support increased protein metabolism for milk production. Higher concentrations of polyamines, such as spermidine and putrescine, were observed postpartum, indicating increased cell growth and improved tissue regeneration. Elevated gamma-aminobutyric acid (GABA) levels during lactation indicate increased microbial activity driven by a nutrient-rich diet. Results showed significant adjustments in bile acid profiles as cows transitioned into lactation. Deoxycholic acid (DCA) remained the predominant BA in feces, reflecting ongoing microbial transformation, while glycine- and taurine-conjugated BA increased postpartum, suggesting improved enterohepatic circulation and lipid absorption. Fecal acylcarnitines showed dynamic shifts with elevated levels during late gestation, a decrease in the dry period, and an increase postpartum, indicating increased fatty acid oxidation to meet energy demands. Results showed that phosphatidylcholines decreased prepartum but increased after calving. This indicates shifts in lipid metabolism reflecting energy requirements in lactation and suggests that fecal lipid composition is an indicator of metabolic adaptations in dairy cows. In particular, PCA revealed cosiderable overlap in the fecal metabolite profiles of multiparous and primiparous cows, indicating similar metabolic profiles. This was also confirmed by volcano plots, which showed no significant differences in fecal metabolism between the 2 groups across different weeks relative to calving (wk -7, -5, -1, +1, +5, +10, +15). Overall, these results emphasize the complex interactions between dietary factors, liver and gastrointestinal function, and the gut microbiome in shaping the fecal metabolite profile of dairy cows. These results underscore the value of this data set in advancing the application of fecal metabolome profiling to investigate metabolic changes during critical transitions in the lactation cycle of dairy cows.PMID:40043758 | DOI:10.3168/jds.2025-26273
Cross-kingdom-mediated detection of intestinal protozoa through NLRP6
Cell Host Microbe. 2025 Feb 26:S1931-3128(25)00056-3. doi: 10.1016/j.chom.2025.02.008. Online ahead of print.ABSTRACTIntestinal protists are detected by the host innate immune system through mechanisms that remain poorly understood. Here, we demonstrate that Tritrichomonas protozoa induce thickening of the colonic mucus in an NLRP6-, ASC-, and caspase-11-dependent manner, consistent with the activation of sentinel goblet cells. Mucus growth is recapitulated with cecal extracts from Tritrichomonas-infected mice but not purified protozoa, suggesting that NLRP6 may detect infection-induced microbial dysbiosis. In agreement, Tritrichomonas infection causes a shift in the microbiota with the expansion of Bacteroides and Prevotella, and untargeted metabolomics reveals a dramatic increase in several classes of metabolites, including sphingolipids. Finally, using a combination of gnotobiotic mice and ex vivo mucus analysis, we demonstrate that wild-type, but not sphingolipid-deficient, B. thetaiotaomicron is sufficient to induce NLRP6-dependent sentinel goblet cell function, with the greatest effect observed in female mice. Thus, we propose that NLRP6 is a sensor of intestinal protozoa infection through monitoring microbial sphingolipids.PMID:40043701 | DOI:10.1016/j.chom.2025.02.008
Trans-zeatin modulates shade stress adaptation in soybean through transcription associated metabolic network
Plant Physiol Biochem. 2025 Feb 22;222:109686. doi: 10.1016/j.plaphy.2025.109686. Online ahead of print.ABSTRACTThis study explores the molecular mechanisms by which trans-zeatin (tZ), a cytokinin, influences shade stress responses in shade-sensitive and shade-tolerant recombinant inbred lines (RILs) 160 and 165 of soybean (Glycine max) under varied light conditions. Using an integrative multi-omics approach combining metabolomics and transcriptomics, we elucidate the regulatory networks underlying soybean adaptation to shade stress. Using an integrative multi-omics approach that combines metabolomics and transcriptomics, we dissect the complex regulatory networks that enable soybean plants to adapt to shade stress. Our results demonstrate that tZ significantly affects growth, biomass accumulation, photosynthetic efficiency, and yield in soybean plants. Metabolomic analysis revealed that shade stress impacts key metabolic pathways, including phenylpropanoids, flavonoids, flavone and flavonol, anthocyanin, and brassinosteroid biosynthesis, with tZ treatment enhances the adaptive responses of soybean plants. Transcriptomic data further identified differential gene expression in these pathways, alongside those related to hormone-mediated signaling pathway, cell wall biogenesis, and defence response pathways underlining the molecular adjustments to tZ and shade stress. Importantly, the integration of metabolomics and transcriptomics data revealed key KEGG pathways and genes regulated by tZ treatment in RIL 160 under shade stress, including significant alterations in phenylpropanoids, flavonoids, hormone-mediated signaling pathway, cell wall biogenesis and defence response, anthocyanin biosynthesis, and fatty acid degradation pathways as well key responsive transcription factors. This study provides insights into the role of tZ in mediating soybean responses to shade stress at the molecular level, offering insights into improving soybean resilience to low light conditions and informing future agricultural practices for optimizing crop yield.PMID:40043461 | DOI:10.1016/j.plaphy.2025.109686
Serum untargeted metabolomics combined with mouse models reveals potential mechanisms of ChengShu QingChu decoction for the treatment of vitiligo
J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Feb 23;1256:124538. doi: 10.1016/j.jchromb.2025.124538. Online ahead of print.ABSTRACTTo illustrate the potential immunological mechanisms of ChengShu QingChu Decoction (CSQC) in vitiligo treatment. An untargeted metabolomic approach was used to detect serum metabolites in 30 patients with progressive vitiligo. Annotation of the differential metabolites were performed using MetaboAnalyst 5.0 and the KEGG database. In addition, 58 Hub genes associated with metabolic pathways were obtained from the GSEA and KEGG databases, and functional enrichment for Hub genes. Finally, it was validated by a mouse model. 102 down-regulated and 86 up-regulated metabolites were detected in serum. The main metabolic pathways enriched for differential metabolites were sphingolipid metabolism and glycerophospholipid metabolism, and the signaling pathways included PI3K-Akt and JAK-STAT signaling pathways, and immune cells included CD56 bright natural killer cell and Central memry CD8 T cell. In the mouse model, a significant decrease in the number of CD8+T cells as well as a decrease in the mRNA expression of JAK1, JAK2, and STAT1 was observed in addition to a trend toward increased melanocytes after drug treatment. This study utilizes metabolomics and bioinformatics analyses, combined with in vivo experimental validation, to elucidate the potential mechanism of CSQC in the treatment of vitiligo.PMID:40043428 | DOI:10.1016/j.jchromb.2025.124538
Transformative potentials, challenges and innovative solutions of lipidomics in multiple clinical applications
Talanta. 2025 Feb 27;291:127855. doi: 10.1016/j.talanta.2025.127855. Online ahead of print.ABSTRACTLipidomics, a rapidly evolving field within metabolomics, provides comprehensive insights into lipid profiles and their roles in health and disease. Advances in lipidomics have enabled the discovery of novel biomarkers with significant clinical applications, revolutionizing the diagnosis, prognosis, and therapeutic monitoring of various diseases. Emerging methodologies, including high-resolution mass spectrometry (HRMS), Ion mobility spectrometry (IMS), and Supercritical Fluid Chromatography (SFC) have enhanced lipid identification and quantification with remarkable analytical whip hands. These advancements are complemented by innovative sample preparation techniques ensuring the recovery of diverse lipid species with minimal degradation. Biomarker discovery with lipidomics has illuminated critical pathways in numerous diseases, including cardiovascular disorders, neurodegenerative conditions, metabolic syndromes, and cancers. Specific lipid classes, such as sphingolipids (SLs) and phospholipids (PLs) have been linked to Alzheimer's disease and diabetes, respectively, while oxylipins and eicosanoids are emerging as inflammatory biomarkers. Furthermore, lipidomic profiles have shown promise in personalized medicine, enabling the stratification of patient sub-populations and tailoring treatment strategies. This review emphasizes the latest innovative developments in analytical technologies, advanced sample preparation techniques and challenges for lipidomics research including bioinformatic tools on multiple clinical conditions. By exploring these cutting-edge developments, this review highlights the transformative potential of lipidomics in biomarker discovery across diverse clinical applications.PMID:40043372 | DOI:10.1016/j.talanta.2025.127855