Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Unaltered maximal power and submaximal performance correlates with an oxidative vastus lateralis proteome phenotype during tapering in male cyclists

Wed, 23/04/2025 - 12:00
Physiol Rep. 2025 Apr;13(8):e70302. doi: 10.14814/phy2.70302.ABSTRACTLittle is known on how a short-term reduction of training volume changes muscle proteome and physiological parameters. We investigated the impact of halving training volume during regular training of cyclists on physiological parameters in relation to vastus lateralis protein profiles and fiber percentage ratios. Fifteen male cyclists (age: 30.1 ± 9.6 yrs.; VO2max: 59.4 ± 4.4 mL∙kg-1∙min-1; weekly training volume: 8.7 ± 2.3 h) participated in an 11-week training intervention. During 2 weeks after a shared training programme for 9 weeks, a control group continued training and a taper group reduced training volume by 50%. No end-point differences were found for peak power output, maximal oxygen uptake, or peak and mean power in a sprint test (p > 0.05), although in the taper group, muscle proteins involved in mitochondrial aerobic respiration increased whereas those involved in translation, protein catabolism, and actin organization decreased, without between-group differences in type I/type II fiber percentage ratios. Tapering did not decrease power at the first (LT1) and second lactate threshold (LT2) compared to t0, whereas power increased in the control group (LT1: 216 ± 28 W vs. 238 ± 11 W, p = 0.042, LT2: 290 ± 42 W vs. 318 ± 13 W, p = 0.005). Our data indicate that transient 50% training volume reductions may be beneficial for oxidative metabolism in muscle.PMID:40265526 | DOI:10.14814/phy2.70302

Elucidating the Neuroprotective Mechanisms of G-3702 in Ischemic Stroke via Integrated Metabolomics and Computational Approaches

Wed, 23/04/2025 - 12:00
CNS Neurosci Ther. 2025 Apr;31(4):e70352. doi: 10.1111/cns.70352.ABSTRACTAIMS: Ischemic stroke (IS) remains a leading cause of disability worldwide, necessitating the development of more effective treatments. While DL-3-n-butylphthalide (NBP) has shown promise in treating IS, its clinical application is limited by hepatotoxicity. G-3702, a structural analog of NBP, has emerged as a potential alternative with reduced hepatotoxicity and proposed pro-angiogenic effects. However, the precise mechanisms underlying G-3702's therapeutic effects in IS remain unclear, hindering its optimization and the identification of novel therapeutic targets. This gap in understanding is particularly significant given the potential of pro-angiogenic treatments to address ischemia-induced vascular damage and improve long-term recovery.METHODS: Here, we employed an integrated approach combining metabolomics, transcriptomics, and machine learning to elucidate G-3702's mechanisms of action in a photothrombotic stroke mouse model. Untargeted metabolomics and pathway analysis explored G-3702's metabolic impacts, while network pharmacology and machine learning algorithms refined key therapeutic target identification. We validated computational insights through immunofluorescence and qPCR experiments.RESULTS: Our results demonstrated that G-3702 significantly improved neurological outcomes and reduced cerebral cortex necrosis in IS mice. Metabolomics implicated the Avb3 integrin pathway in G-3702's pro-angiogenic effects, while computational analyses highlighted the PI3K-Akt and HIF-1α pathways as central to this action. Machine learning algorithms prioritized potential biomarkers and targets, including BDNF, FGF2, ITGAV, ITGB3, SRC, and RHOA. Immunofluorescence confirmed enhanced angiogenesis, and qPCR demonstrated increased expression of these angiogenesis-related genes following G-3702 treatment.CONCLUSION: These findings suggest that G-3702 promotes angiogenesis in the ischemic brain area primarily via the Avb3 integrin pathway, offering a mechanistic explanation for its therapeutic effects in IS. By elucidating G-3702's mode of action, this study not only enhances its clinical potential but also contributes to the broader field of stroke treatment by identifying novel therapeutic targets. Our integrated approach to mechanism elucidation advances the understanding of pro-angiogenic treatments for stroke and may serve as a model for future drug development efforts in IS and other complex neurological disorders. Ultimately, this work enhances G-3702's potential for clinical translation as an improved stroke therapy and opens new avenues for optimizing post-stroke recovery.PMID:40265291 | DOI:10.1111/cns.70352

Characterising functional redundancy in microbiome communities via relative entropy

Wed, 23/04/2025 - 12:00
Comput Struct Biotechnol J. 2025 Mar 12;27:1482-1497. doi: 10.1016/j.csbj.2025.03.012. eCollection 2025.ABSTRACTFunctional redundancy has been hypothesised to be at the core of the well-evidenced relation between high ecological microbiome diversity and human health. Here, we conceptualise and operationalise functional redundancy on a single-trait level for functionally annotated microbial communities, utilising an information-theoretic approach based on relative entropy that also allows for the quantification of functional interdependency across species. Via constraint-based microbiome community modelling of a public faecal metagenomic dataset, we demonstrate that the strength of the relation between species diversity and functional redundancy is dependent on specific attributes of the function under consideration such as the rarity and the occurring functional interdependencies. Moreover, by integrating faecal metabolome data, we highlight that measures of functional redundancy have correlates in the host's metabolome. We further demonstrate that microbiomes sampled from colorectal cancer patients display higher levels of species-species functional interdependencies than those of healthy controls. By analysing microbiome community models from an inflammatory bowel disease (IBD) study, we show that although species diversity decreased in IBD subjects, functional redundancy increased for certain metabolites, notably hydrogen sulphide. This finding highlights their potential to provide valuable insights beyond species diversity. Here, we formalise the concept of functional redundancy in microbial communities and demonstrate its usefulness in real microbiome data, providing a foundation for a deeper understanding of how microbiome diversity shapes the functional capacities of a microbiome.PMID:40265160 | PMC:PMC12013412 | DOI:10.1016/j.csbj.2025.03.012

Tea polyphenol mediated <em>CsMYB77</em> regulation of <em>CsPOD44</em> to promote tea plant (<em>Camellia sinensis</em>) root drought resistance

Wed, 23/04/2025 - 12:00
Hortic Res. 2025 Feb 18;12(6):uhaf048. doi: 10.1093/hr/uhaf048. eCollection 2025 Jun.ABSTRACTDrought stress significantly alters the metabolic homeostasis of tea plants; however, few studies have examined the role of specific metabolites, particularly tea polyphenols, in drought resistance. This study reveals that the tea polyphenol content in drought-tolerant tea cultivars tends to increase under drought conditions. Notably, in environments characterized by staged and repeated drought, changes in tea polyphenol are significantly positively correlated with drought resistance. To investigate this further, we irrigated the roots with exogenous tea polyphenols before subjecting the plants to drought. Our findings indicated that the absorptive roots of the experimental group exhibited enhanced development, improved cellular integrity, and a significant increase in peroxidase activity. A comprehensive analysis of the transcriptome and metabolome revealed that tea polyphenols are closely associated with the phenylpropanoid metabolism pathway. Notably, CsMYB77 and CsPOD44 genes were identified as highly correlated with this pathway. Overexpression experiments in Arabidopsis thaliana demonstrated that CsMYB77 promotes the expression of phenylpropanoid pathway genes, thereby enhancing drought resistance. Conversely, antisense oligonucleotide silencing of CsMYB77 decreased drought resistance in tea plants. Additional experiments, including yeast one-hybrid assays, luciferase complementation imaging, dual-luciferase assays, and electrophoretic mobility shift assays, confirmed that CsMYB77 positively regulates the expression of CsPOD44. In summary, our findings indicate that the differences in drought tolerance among tea cultivars are closely linked to phenylpropanoid metabolism. Specifically, tea polyphenols may mediate the regulatory network involving CsMYB77 and CsPOD44, thereby enhancing stress resistance by promoting root development. This study offers new insights into the breeding of drought-resistant tea cultivars.PMID:40265128 | PMC:PMC12010877 | DOI:10.1093/hr/uhaf048

Indoleamine 2,3-dioxygenase 1-mediated immune suppressive status is positively associated with brain metastasis in patients with non-small cell lung cancer

Wed, 23/04/2025 - 12:00
J Natl Cancer Cent. 2024 Dec 15;5(2):179-192. doi: 10.1016/j.jncc.2024.12.004. eCollection 2025 Apr.ABSTRACTBACKGROUND: Indoleamine 2,3-dioxygenase (IDO1) activity, measured by kynurenine/tryptophan (K:T) ratio, is known for its association with distant metastasis and overall survival (OS) in patients with non-small cell lung cancer (NSCLC). Here, we aimed to examine whether IDO1 activity is correlated with OS in NSCLC patients with brain metastasis (Bramet) and has negative effect on modulating the anti-tumor functions of immune cells.METHODS: This study was a part of a prospective clinical trial in circulating biomarkers. Blood or tissues from eligible participants were collected for measurement of kynurenine, tryptophan, immune cell subtype, scRNA-seq analysis, and untargeted metabolomics analysis.RESULTS: A total of 195 patients were enrolled. The median kynurenine to tryptophan (K:T) ratio was 0.18, with consistent values observed among patients with NSCLC Bramet and those without (0.18 and 0.11, respectively). Notably, student's t-test analysis revealed significantly higher kynurenine concentrations in stage IV patients compared to those in stage I (2.3 vs 1.7 µM, P < 0.001). In patients with Bramet, both kynurenine concentrations and K:T ratios were significantly elevated in comparison with those of extra-cerebral metastasis (2.7 vs 1.9 µM, P < 0.001; 0.12 vs 0.095, P = 0.028; respectively). Single-cell analysis further validated a high level of IDO1 expression in stage IV tumors or Bramet lesions, particularly in macrophages, regulated by chemokines such as CXCL11. Additionally, K:T ratios exhibited significant associations with Treg cell percentages and OS in patients with Bramet (P = 0.039). Treatment with kynurenine led to the upregulation of immune-suppressive molecules, including PD-1, in T cells. Finally, untargeted metabolomics analysis further identified that, apart from the IDO1 metabolic pathway, other metabolites, such as those involved in phospholipid pathways, were also implicated in Bramet.CONCLUSION: IDO1 metabolites may play immune-suppressive roles in NSCLC patients with Bramet.PMID:40265090 | PMC:PMC12010389 | DOI:10.1016/j.jncc.2024.12.004

Editorial: Metabolomics in personalized cancer medicine

Wed, 23/04/2025 - 12:00
Front Mol Biosci. 2025 Apr 8;12:1593877. doi: 10.3389/fmolb.2025.1593877. eCollection 2025.NO ABSTRACTPMID:40264954 | PMC:PMC12011556 | DOI:10.3389/fmolb.2025.1593877

An approach of molecular-fingerprint prediction implementing a GAT

Wed, 23/04/2025 - 12:00
RSC Adv. 2025 Apr 22;15(16):12757-12764. doi: 10.1039/d5ra00973a. eCollection 2025 Apr 16.ABSTRACTIn the domain of metabolomics, the accurate identification of compounds is paramount. However, this process is hindered by the vast number of metabolites, which poses a significant challenge. In this study, a novel approach to compound identification is proposed, namely a molecular-fingerprint prediction method based on the graph attention network (GAT) model. The method involves the processing of fragmentation-tree data derived from tandem mass spectrometry (MS/MS) data computation and the subsequent processing of fragmentation-tree graph data with a technique inspired by natural language processing. The model is then trained using a 3-layer GAT model and a 2-layer linear layer. The results demonstrate the method's efficacy in molecular-fingerprint prediction, with the prediction of molecular fingerprints from MS/MS spectra exhibiting a high degree of accuracy. Firstly, this model achieves excellent performance in receiver operating characteristic (ROC) and precision-recall curves. The factors that have the most influence on the resultant performance are identified as edge features using different training parameters. Then, better performance is achieved for accuracy and F 1 score in comparison with MetFID. Secondly, the model performance was validated by querying the molecular libraries through methods commonly used in related studies. In the results based on precursor mass querying, the proposed model achieves comparable performance with CFM-ID; in the results based on molecular formula querying, the model achieves better performance than MetFID. This study demonstrates the potential of the GAT model for compound identification tasks and provides directions for further research.PMID:40264881 | PMC:PMC12013609 | DOI:10.1039/d5ra00973a

Pancreatic cancer subtyping - the keystone of precision treatment

Wed, 23/04/2025 - 12:00
Front Immunol. 2025 Apr 8;16:1563725. doi: 10.3389/fimmu.2025.1563725. eCollection 2025.ABSTRACTIn recent years, the incidence and mortality rates of pancreatic cancer have been rising, posing a severe threat to human health. Tumor heterogeneity remains a critical barrier to advancing diagnosis and treatment efforts. The lack of specific early symptoms, limited early diagnostic methods, high biological complexity, and restricted therapeutic options contribute to the poor outcomes and prognosis of pancreatic cancer. Therefore, there is an urgent need to explore the different subtypes in-depth and develop personalized therapeutic strategies tailored to each subtype. Increasing evidence highlights the pivotal role of molecular subtyping in treating pancreatic cancer. This review focuses on recent advancements in classifying molecular subtypes and therapeutic approaches, discussed from the perspectives of gene mutations, genomics, transcriptomics, proteomics, metabolomics, and immunomics.PMID:40264765 | PMC:PMC12011869 | DOI:10.3389/fimmu.2025.1563725

Addressing the tissue specificity of U5 snRNP spliceosomopathies

Wed, 23/04/2025 - 12:00
Front Cell Dev Biol. 2025 Apr 8;13:1572188. doi: 10.3389/fcell.2025.1572188. eCollection 2025.ABSTRACTPrecursor mRNA (pre-mRNA) must undergo splicing to remove intron sequences and join exons. This splicing process is catalysed by an RNA/protein complex called the spliceosome. At the centre of the catalytic spliceosome is the U5 small nuclear ribonucleoprotein (snRNP). Pathogenic variants in U5 snRNP core proteins are associated with various diseases commonly known as spliceosomopathies. Variants in TXNL4A and EFTUD2 manifest in craniofacial malformations while variants in PRPF8 and SNRNP200 manifest in retinitis pigmentosa. This perspective highlights research addressing how these specific manifestations come about as the spliceosome is required in all cells and at all developmental stages. Cell and animal models can replicate the human clinical specificity providing explanations for the specificity of the disorders. We propose that future research could benefit from models originating from patient-derived induced pluripotent stem cells (iPSCs) and isogenic controls to compare the coding and non-coding transcriptomic perturbations. Analysis of spliceosomal protein complexes and their interactome could also uncover novel insights on molecular pathogenesis. Finally, as studies highlight changes in metabolic processes, metabolomic studies could become a new venture in studying the consequences of U5 snRNP variants.PMID:40264708 | PMC:PMC12011746 | DOI:10.3389/fcell.2025.1572188

<em>Vaccinium myrtillus</em> L. ameliorates diabetic nephropathy via modulating metabolites and gut microbiota in rats

Wed, 23/04/2025 - 12:00
Front Pharmacol. 2025 Apr 8;16:1541947. doi: 10.3389/fphar.2025.1541947. eCollection 2025.ABSTRACTINTRODUCTION: Diabetic nephropathy (DN), one of the serious complications in the diabetes, has a high mortality in the diabetic patients. Bilberry (Vaccinium myrtillus L.) have received much attention for their health benefits in alleviating metabolic diseases, which are rich in anthocyanins. However, the anti-DN ability of bilberry has not been fully studied. The aim of this study was to investigate the effect and mechanism of Vaccinium myrtillus L. extract (VCE) on diabetic nephropathy in vivo and in vitro.METHODS: Streptozocin (STZ) combined with high fat induced DN model was established in rats. Biochemical indicators, histopathology, 16s third generation sequencing and serum metabolomics were used to evaluate the effects of VCE on DN. Subsequently, a cell model of advanced glycation end products (AGEs) induced podocyte injury was established to verify which compounds in VCE played the main anti-diabetic nephropathy function and the mechanism of action. Finally, in vitro experiments were conducted to verify the effect of characteristic metabolites screened by serum metabolomics on improving diabetic nephropathy.RESULTS: Insulin resistance index, lipid metabolism, oxidative stress and inflammatory response indexes of DN rats were significantly improved after 8 weeks of VCE treatment. In addition, intake of VCE modulates gut microbiota composition and reverses the abundance of Lactobacillus, Bifidobacterium and Ruminococcus. Supplementation with VCE altered serum metabolite levels, including uridine and phenylacetylglycine. Pretreatment with VCE and its anthocyanins inhibited the expression of LDH, IL-6 and TNF-α, reduced the levels of p38-MAPK, IĸBα, IKKβ, and NF-κB in podocyte cells. In addition, pretreatment with serum metabolite uridine also reduced the expression of LDH and mitochondrial ROS, and inhibited cell apoptosis.CONCLUSION: Our findings suggest that the improvement of gut microbiota and metabolic function were related to the anti-DN potential of VCE, and the underlying mechanism may be related to the inhibition of MAPK/NF-κB signaling pathway.PMID:40264677 | PMC:PMC12011793 | DOI:10.3389/fphar.2025.1541947

Characterizing flavor determinants and α-glucosidase inhibitory components in ancient tea plants and '<em>Qiancha 1</em>' white teas

Wed, 23/04/2025 - 12:00
Food Chem X. 2025 Mar 25;27:102408. doi: 10.1016/j.fochx.2025.102408. eCollection 2025 Apr.ABSTRACTThis study aimed to compare white teas derived from ancient tea plants (AT) and the cultivar 'Qiancha 1' (QC1) using multi-omics approaches, focusing on differences in volatile/non-volatile components, sensory traits, and α-glucosidase inhibitory activity. Both teas shared sweet aromas and mellow tastes, but AT exhibited significantly stronger floral intensity (p < 0.05), whereas QC1 dominated in citrus/fruity aroma. GC-olfactometry and chemometric modeling identified six key metabolites, with trans-β-ionone (rOAV = 149.6) and β-damascenone (rOAV = 47.6) driving floral and citrus/fruity characteristics, respectively. Targeted metabolomics revealed significantly higher levels of ester-catechins, caffeine, and gallic acid in AT. These compounds exhibited significant dose-response correlations with bitterness, astringency, and α-glucosidase inhibitory activity (r = 0.83-0.93, p < 0.05), suggesting their dual role in flavor enhancement and hypoglycemic potential. This work provides scientific evidence and technical insights for the high-value utilization of ancient tea plants resources and the optimization of white tea processing technologies.PMID:40264443 | PMC:PMC12013395 | DOI:10.1016/j.fochx.2025.102408

Spatially Resolved Metabolomics Reveals Metabolic Heterogeneity Among Pulmonary Fibrosis

Wed, 23/04/2025 - 12:00
J Mass Spectrom. 2025 May;60(5):e5138. doi: 10.1002/jms.5138.ABSTRACTPulmonary fibrosis (PF) is a chronic and progressive lung disease with fatal consequences. The study of PF is challenging due to the complex mechanism involved, the need to understand the heterogeneity and spatial organization within lung tissues. In this study, we investigate the metabolic heterogeneity between two forms of lung fibrosis: idiopathic pulmonary fibrosis (IPF) and silicosis, using advanced spatially-resolved metabolomics techniques. Employing high-resolution mass spectrometry imaging, we spatially mapped and identified over 260 metabolites in lung tissue sections from mouse models of IPF and silicosis. Histological analysis confirmed fibrosis in both models, with distinct pathological features: alveolar destruction and collagen deposition in IPF, and nodule formation in silicosis. Metabolomic analysis revealed significant differences between IPF and silicosis in key metabolic pathways, including phospholipid metabolism, purine/pyrimidine metabolism, and the TCA cycle. Notably, phosphocholine was elevated in silicosis but reduced in IPF, while carnitine levels decreased in both conditions. Additionally, glycolytic activity was increased in both models, but TCA cycle intermediates showed opposing trends. These findings highlight the spatial metabolic heterogeneity of PF and suggest potential metabolic targets for therapeutic intervention. Further investigation into the regulatory mechanisms behind these metabolic shifts may open new avenues for fibrosis treatment.PMID:40264277 | DOI:10.1002/jms.5138

Sexual dimorphism in metabolomic and phenotypic spectra of UGT deficiency: findings from the Canadian Longitudinal Study on Aging

Wed, 23/04/2025 - 12:00
Biol Sex Differ. 2025 Apr 22;16(1):26. doi: 10.1186/s13293-025-00708-5.ABSTRACTBACKGROUND: Two of the most frequently deleted genes in the human genome are the UDP-glycosyltransferases UGT2B17 and UGT2B28. They encode metabolic enzymes of the glucuronidation pathway that plays a pivotal role in the maintenance of cellular homeostasis for a variety of small molecule metabolites. These deletions may impact health, yet their effects remain poorly understood. We evaluated the impact of UGT deficiency on the plasma metabolome and examined the association between altered metabolites and health outcomes.METHODS: The metabolomic profiles of 4262 proficient gene carriers were compared with those of 352 UGT2B17-deficient, 97 UGT2B28-deficient, and 20 double-gene-deficient individuals from the Canadian Longitudinal Study on Aging. Significant metabolites found in these comparisons were analyzed for their associations with common diseases.RESULTS: The unexpectedly broad molecular divergence found in UGT-deficient metabolomes, which affected > 10% of metabolites, implies their significant influence across various metabolite classes-particularly lipids and amino acids - extending beyond their known substrates. The metabolic profiles of UGT2B17-deficient men and UGT2B28-deficient women were most impacted, with UGT2B17 deficiency affecting various metabolites linked to metabolic diseases, arthritis, and osteoporosis. Metabolites impacted by a UGT2B28 deficiency such as amino acids, were linked to metabolic disorders in women.CONCLUSION: The findings significantly advance our understanding of the metabolic landscape associated with these frequently deleted genes in the human genome, which may influence susceptibility to various diseases in a sex-specific manner, laying the groundwork for determining their pathological mechanisms and impact on human health.PMID:40264209 | DOI:10.1186/s13293-025-00708-5

Glucose- and glutamine-driven de novo nucleotide synthesis facilitates WSSV replication in shrimp

Wed, 23/04/2025 - 12:00
Cell Commun Signal. 2025 Apr 22;23(1):191. doi: 10.1186/s12964-025-02186-z.ABSTRACTBACKGROUND: Viruses rely on host metabolism to complete their replication cycle. White spot syndrome virus (WSSV), a major pathogen in shrimp aquaculture, hijacks host metabolic pathways to fulfill its biosynthetic and energetic needs. Previous studies have demonstrated that WSSV promotes aerobic glycolysis (Warburg effect) and glutaminolysis during its replication stage (12 hpi). Therefore, glucose and glutamine serve as crucial metabolites for viral replication. Additionally, de novo nucleotide synthesis, including the pentose phosphate pathway and purine/pyrimidine synthesis, is significantly activated during WSSV infection. However, the precise association between WSSV and host glucose and glutamine metabolism in driving de novo nucleotide synthesis remains unclear. This study aimed to investigate the involvement of glucose and glutamine in nucleotide metabolism during WSSV replication and to elucidate how WSSV reprograms these pathways to facilitate its pathogenesis.METHODS: To assess changes in metabolic flux during WSSV replication, LC-ESI-MS-based isotopically labeled glucose ([U-13C] glucose) and glutamine ([A-15N] glutamine) were used as metabolic tracers in in vivo experiments with white shrimp (Litopenaeus vannamei). The in vivo experiments were also conducted to measure the expression and enzymatic activity of genes involved in nucleotide metabolism. Additionally, in vivo dsRNA-mediated gene silencing was employed to evaluate the roles of these genes in WSSV replication. Pharmacological inhibitors targeting the Ras-PI3K-Akt-mTOR pathway were also applied to investigate its regulatory role in WSSV-induced nucleotide metabolic reprogramming.RESULTS: The metabolite tracking analysis confirmed that de novo nucleotide synthesis was significantly activated at the WSSV replication stage (12 hpi). Glucose metabolism is preferentially reprogrammed to support purine synthesis, while glutamine uptake is significantly increased and contributes to both purine and pyrimidine synthesis. Consistently, gene expression and enzymatic activity analyses, along with gene silencing experiments, indicated the critical role of de novo nucleotide synthesis in supporting viral replication. However, while the inhibition of the Ras-PI3K-Akt-mTOR pathway suggested its involvement in regulating nucleotide metabolism, no consistent effect on WSSV replication was observed, suggesting the presence of alternative regulatory mechanisms.CONCLUSION: This study demonstrates that WSSV infection induces specific metabolic reprogramming of glucose and glutamine utilization to facilitate de novo nucleotide synthesis in shrimp. These metabolic changes provide the necessary precursors for nucleotide synthesis, supporting WSSV replication and pathogenesis. The findings offer novel insights into the metabolic strategies employed by WSSV and suggest potential targets for controlling WSSV outbreaks in shrimp aquaculture.PMID:40264189 | DOI:10.1186/s12964-025-02186-z

The single degree of polymerization influences the efficacy of xylooligosaccharides in shaping microbial and metabolite profiles in chicken gut to combat avian pathogenic Escherichia coli

Wed, 23/04/2025 - 12:00
BMC Microbiol. 2025 Apr 22;25(1):227. doi: 10.1186/s12866-025-03948-y.ABSTRACTBACKGROUND: Avian pathogenic Escherichia coli (APEC) threatens both poultry production and human health. Xylooligosaccharides (XOS) may suppress pathogenic bacteria through prebiotic actions. However, the influences of single degree of polymerization (DP) on the inhibition of APEC by XOS remain unknown. This study aimed to probe if XOS and their major monomers (xylobiose, xylotriose and xylotetraose) could differentially combat APEC via prebiotic actions using an in vitro fermentation model with chicken cecal microbiota.METHODS: Microbiota were randomly divided into 7 groups (5 replicate tubes/group). Control group (CON) received no treatment; XOS group received commercial XOS mixtures; APEC group received APEC; XA, X2, X3 and X4 groups received APEC combined with commercial XOS mixtures, xylobiose, xylotriose and xylotetraose, respectively.RESULTS: XOS and their major monomers mitigated APEC-induced decline (p < 0.05) in gut microbial α-diversity, with xylotetrose showing the least effect. Gut microbiota in XA, X2, X3 and X4 groups clustered together, with a relative separation observed in X4 group. XOS and their monomers elevated (p < 0.05) the abundances of Firmicutes, Bacteroidota and several probiotics (Lactobacillus, Bacteroides and Megamonas), but reduced (p < 0.05) the abundances of Proteobacteria and Escherichia-Shigella, with xylotetraose exhibiting the least efficacy. Besides, xylotriose and xylotetrose had an advantage over xylotetraose in promoting microbial production of short-chain fatty acids. Metabolomics analysis revealed that APEC challenge mainly downregulated (p < 0.05) several amino acids metabolism pathways of gut microbiota, while xylotriose had an inferiority to XOS in upregulating (p < 0.05) histidine metabolism pathway. Furthermore, microbial fermentation metabolites of all XOS monomers lowered (p < 0.05) certain virulence genes expression in APEC, with xylotriose being the most advantageous.CONCLUSIONS: XOS and their major monomers differentially improved gut microbiota and metabolite profiles in chicken gut against APEC challenge. Overall, xylotriose exhibited the greatest inhibition against APEC abundance and virulence. Our findings underscore the role of single DP in influencing the prebiotic actions of XOS against APEC, providing a basis for the reasonable application of XOS in diets to combat bacterial challenge.PMID:40264018 | DOI:10.1186/s12866-025-03948-y

In vitro human gastrointestinal digestibility and colonic fermentation of edible yeast-based protein: A comparative study with whey and casein

Wed, 23/04/2025 - 12:00
Food Res Int. 2025 May;208:116098. doi: 10.1016/j.foodres.2025.116098. Epub 2025 Feb 25.ABSTRACTThe global protein demand is in constant increase requiring sustainable and healthier alternative proteins for animal and human nutrition. Yeast-based proteins (YBP) represent a non-negligible environmental-friendly fermentation-based solutions with high nutritional quality and bioavailability. Although in vitro studies cannot reflect the full complexity of in vivo digestion, it is considered as useful alternatives to animal models assessing protein digestibility. A 5 h TIM-1 digestion model (TNO Gastro-Intestinal Model) was used to assess the digestibility profile and amino acid bio-accessibility of YBP (3 separate production batches) versus whey and casein as references. Every hour, dialysate and ileal effluent samples were collected. Total nitrogen and free amino acid (FAA) were quantified. To assess the microbial impact, YBP digestate was subjected to 48 h Colon-on-a-Plate batch fermentation, after which the microbial composition by shotgun sequencing and microbial activity by Short-Chain Fatty Acids (SCFAs), Branched-Chain Fatty Acids (BCFAs) (GC-MS) and untargeted metabolomics (LA-REIMS) was analysed (from N = 11 healthy donors of faecal material). YBP, casein and whey were comparable in terms of digestibility. Although YBP showed a different metabolomic fingerprint compared to casein and whey, the microbial activity through SCFA quantification was significantly increased for all proteins compared to blank but not between protein sources. Whey and casein resulted in a higher abundance of Clostridium compared to YBP, while the treatment with YBP resulted in higher abundance of Bacteroides. Altogether, our results suggest that YBP could be a nutritionally relevant alternative protein.PMID:40263880 | DOI:10.1016/j.foodres.2025.116098

Integrated multi-omics uncover viruses, active fermenting microbes and their metabolic profiles in the Daqu microbiome

Wed, 23/04/2025 - 12:00
Food Res Int. 2025 May;208:116061. doi: 10.1016/j.foodres.2025.116061. Epub 2025 Feb 27.ABSTRACTThe coexistence and coevolution of viruses and fermenting microbes have a significant impact on the structure and function of microbial communities. Although the presence of viruses in Daqu, the fermentation starter for Chinese Baijiu, has been documented, their specific effects on the community composition and metabolic functions of low, medium, and high-temperature Daqu remain unclear. In this study, we employed multi-omics technology to explore the distribution of viruses and active bacteria and fungi in various Daqu and their potential metabolic roles. Viral metagenomic sequencing showed a predominance of Parvoviridae in High-Temperature Daqu (HTQ), while Genomoviridae were dominant in Medium-Temperature Daqu (MTQ) and Low- Temperature Daqu (LTQ). Phages belonging to the Siphoviridae, Podoviridae, Herelleviridae, and Myoviridae families showed significantly different abundances across three Daqu groups. Metatranscriptomic analysis showed that fungal communities were most active in LTQ, whereas bacterial communities were dominant in MTQ and HTQ. By employing the CRISPR-Cas spacer, a higher predicted number of phage-host linkages was identified in LTQ, particularly with hosts including Lactobacillus, Staphylococcus, Acinetobacter, Enterobacter, and Bacillus. Correlation analysis showed that bacteria like Acinetobacter, Lactobacillus, and Streptococcus exhibited the strongest associations with metabolites, particularly amino acids and organic acids. The potential phage-induced metabolic differences in the three Daqu groups were mainly linked to pathways involved in the metabolism of amino acids, sugars, and organic acids. Overall, our study elucidates the impact of viruses on shaping microbial composition and influencing metabolic functions in Daqu. These results improve our comprehension of viruses and microbes in Daqu microbial communities and provide valuable insights for enhancing quality control in Daqu production.PMID:40263874 | DOI:10.1016/j.foodres.2025.116061

Impact of processing methods in shaping taste, flavor, antioxidants, and metabolites in teas (Camellia sinensis): A multi-method analysis

Wed, 23/04/2025 - 12:00
Food Res Int. 2025 May;208:116060. doi: 10.1016/j.foodres.2025.116060. Epub 2025 Mar 8.ABSTRACTThis study systematically examined the effects of processing techniques on the flavor profiles and functional attributes of tea derived from fresh leaves (Camellia sinensis) of identical origin. Pu-erh raw tea (PRT), white tea (WT), and black tea (BT) were produced through distinct processing protocols (non-fermented, lightly fermented, and fully fermented, respectively). Antioxidant activity and sensory characteristics were evaluated alongside comprehensive metabolomic analyses using GC-IMS, GC-MS, and UHPLC-QTOF-MS. PRT exhibited superior antioxidant capacity with pronounced bitterness and astringency, whereas WT displayed fruity-sweet notes and BT demonstrated a mellow profile linked to fermentation. Metabolomic profiling identified six discriminative biomarkers and two pivotal compounds differentiating tea types, alongside six key metabolic pathways (e.g., secondary metabolite biosynthesis) driving compositional variations. These findings elucidate processing-induced biochemical transformations, offering insights for quality optimization and consumer-oriented tea selection.PMID:40263873 | DOI:10.1016/j.foodres.2025.116060

How to sample Listeria monocytogenes culture for volatolomics by headspace extraction-gas chromatography-Q Exactive-Orbitrap mass spectrometry?

Wed, 23/04/2025 - 12:00
Food Res Int. 2025 May;208:116043. doi: 10.1016/j.foodres.2025.116043. Epub 2025 Feb 24.ABSTRACTVolatolomics - branch of metabolomics focused on volatile organic compounds (VOCs) - provides a wealth of information for characterizing foodborne pathogens and their behavior. But there is no knowledge relating on how to sample microbial VOCs. The aim of the present study was to determine the most informative sampling mode for further volatolomics. Taking Listeria monocytogenes (L.monocytogenes) as a model pathogen and using case-control experiments based on 0-24 h cultures on liquid synthetic growth medium, bacteria volatolomics was performed by headspace solid phase microextraction - gas chromatography - Q Exactive - Orbitrap ™ mass spectrometry on three types of samples: (i) the whole culture, which contains global information diluted by the growth medium, (ii) the pellet collected after centrifugation of the whole culture, which concentrates bacterial cells; and (iii) the related supernatant which includes what the bacteria released into the growth medium. Compound Discoverer ™ software was used for automatic peak deconvolution of VOCs. The three sampling modes resulted in different and complementary L.monocytogenes candidate VOC markers: whole culture and pellet together cover 83 % of the candidate markers, while supernatant and supernatant-pellet combination reveal only 59 % and 74 %, respectively. The robustness of the candidate VOC markers identified together with the relevance of combining the different sampling modes are discussed.PMID:40263872 | DOI:10.1016/j.foodres.2025.116043

Effects of chitosan on restoring spermatogenesis in mice: Insights from gut microbiota and multi-omics analysis

Wed, 23/04/2025 - 12:00
Food Res Int. 2025 May;208:116218. doi: 10.1016/j.foodres.2025.116218. Epub 2025 Mar 14.ABSTRACTChitosan, is a natural bio-based polymer with known prebiotic properties. However, its potential in the management of spermatogenic disorders remains largely unexplored. By utilizing a busulfan-treated mouse model and integrated multi-omics analysis, this study explored the potential mechanisms through which chitosan improves impaired spermatogenesis. The results showed that chitosan treatment can improve testicular function and significantly reshape the gut microbiota composition in busulfan-treated mice. Metabolomics revealed that docosahexaenoic acid (DHA) transport was significantly dysregulated in busulfan-treated mice, but chitosan reversed this dysfunction by modulating tight junction proteins and fatty acid transporters in the intestine. Fecal microbiota transplantation experiments further highlighted the critical role of gut microbiota in DHA transport and spermatogenesis. Additionally, DHA supplementation alleviated busulfan-induced ferroptosis in testicular tissues. Hence, owing to its prebiotic effects chitosan could serve as a novel therapeutic strategy for improving busulfan-induced spermatogenic disorders by restoring the homeostasis of the gut-testis axis.PMID:40263850 | DOI:10.1016/j.foodres.2025.116218

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