PubMed

Commun Biol. 2025 Mar 11;8(1):410. doi: 10.1038/s42003-025-07828-z.ABSTRACTMethylmalonic aciduria (MMA) is an inborn error of metabolism resulting in loss of function of the enzyme methylmalonyl-CoA mutase (MMUT). Despite acute and persistent neurological symptoms, the pathogenesis of MMA in the central nervous system is poorly understood, which has contributed to a dearth of effective brain specific treatments. Here we utilised patient-derived induced pluripotent stem cells and in vitro differentiation to generate a human neuronal model of MMA. We reveal strong evidence of mitochondrial dysfunction caused by deficiency of MMUT in patient neurons. By employing patch-clamp electrophysiology, targeted metabolomics, and bulk transcriptomics, we expose an altered state of excitability, which is exacerbated by application of dimethyl-2-oxoglutarate, and we suggest may be connected to metabolic rewiring. Our work provides first evidence of mitochondrial driven neuronal dysfunction in MMA, which through our comprehensive characterisation of this paradigmatic model, enables first steps to identifying effective therapies.PMID:40069408 | DOI:10.1038/s42003-025-07828-z

Sci Rep. 2025 Mar 12;15(1):8470. doi: 10.1038/s41598-025-92840-w.ABSTRACTThe purpose of this study was to find metabolic changes associated with incident hypertension in the volunteer-based Estonian Biobank. We used a subcohort of the Estonian Biobank where metabolite levels had been measured by mass-spectrometry (LC-MS, Metabolon platform). We divided annotated metabolites of 989 individuals into KEGG pathways, followed by principal component analysis of metabolites in each pathway, resulting in a dataset of 91 pathway components. Next, we defined incident hypertension cases and controls based on electronic health records, resulting in a dataset of 101 incident hypertension cases and 450 controls. We used Cox proportional hazards models and replicated the results in a separate cohort of the Estonian Biobank, assayed with LC-MS dataset of the Broad platform and including 582 individuals. Our results show that body mass index and a component of the carbon metabolism KEGG pathway are associated with incident hypertension in both discovery and replication cohorts. We demonstrate that a high-dimensional dataset can be meaningfully reduced into informative pathway components that can subsequently be analysed in an interpretable way, and replicated in a metabolomics dataset from a different platform.PMID:40069276 | DOI:10.1038/s41598-025-92840-w

Sci Rep. 2025 Mar 11;15(1):8442. doi: 10.1038/s41598-025-92189-0.ABSTRACTThe diagnosis of Lyme neuroborreliosis (LNB) requires the demonstration of intrathecal synthesis of Borrelia antibodies in a patient's cerebrospinal fluid (CSF), which involves the invasive procedure of a lumbar puncture. This study serves as a feasibility study aimed at exploring the potential of using serum samples, which are easily obtainable routine clinical samples, for LNB diagnostics via advanced metabolomics techniques. Serum samples were collected from confirmed LNB patients before and after treatment, with post-treatment samples serving as controls. The objective of the study was to find stable biomarkers for acute LNB through untargeted metabolomics analysis using ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The study focused on biomarkers that could be reliably detected in serum samples stored under typical clinical conditions, without the need for special handling, ensuring consistent detection over time. The analysis revealed 26,978 molecular features (MFs), of which 1,746 were statistically significant (p < 0.001). Further manual investigation into 91 of the most prominent MFs revealed 53 potential biomarkers for LNB, individually or in combination. The workflow developed provides a comprehensive platform for biomarker detection, with potential applications in both research and clinical settings for LNB and other infections. This minimally invasive diagnostic approach is promising, and additional validation and future studies are needed for it to be considered as a practical alternative or a complement to CSF-based diagnostics of LNB in everyday clinical practice.PMID:40069240 | DOI:10.1038/s41598-025-92189-0

Gut Microbes. 2025 Dec;17(1):2474141. doi: 10.1080/19490976.2025.2474141. Epub 2025 Mar 11.ABSTRACTDespite extensive investigations into the microbiome and metabolome changes associated with colon polyps and colorectal cancer (CRC), the microbiome and metabolome profiles of individuals with colonic polyposis, including those with (Gene-pos) and without (Gene-neg) a known genetic driver, remain comparatively unexplored. Using colon biopsies, polyps, and stool from patients with Gene-pos adenomatous polyposis (N = 9), Gene-neg adenomatous polyposis (N = 18), and serrated polyposis syndrome (SPS, N = 11), we demonstrated through 16S rRNA sequencing that the mucosa-associated microbiota in individuals with colonic polyposis is representative of the microbiota associated with small polyps, and that both Gene-pos and SPS cohorts exhibit differential microbiota populations relative to Gene-neg polyposis cohorts. Furthermore, we used these differential microbiota taxa to perform linear discriminant analysis to differentiate Gene-neg subjects from Gene-pos and from SPS subjects with an accuracy of 89% and 93% respectively. Stool metabolites were quantified via 1H NMR, revealing an increase in alanine in SPS subjects relative to non-polyposis subjects, and Partial Least Squares Discriminant Analysis (PLS-DA) analysis indicated that the proportion of leucine to tyrosine in fecal samples may be predictive of SPS. Use of these microbial and metabolomic signatures may allow for better diagnostric and risk-stratification tools for colonic polyposis patients and their families as well as promote development of microbiome-targeted approaches for polyp prevention.PMID:40069167 | DOI:10.1080/19490976.2025.2474141

Int J Biol Macromol. 2025 Mar 9:141899. doi: 10.1016/j.ijbiomac.2025.141899. Online ahead of print.ABSTRACTInflammation significantly influences the development of gastrointestinal (GI) diseases such as inflammatory bowel diseases (IBD)and ulcerative colitis, which disrupts normal digestive functions, leading to tissue damage and various symptoms. This research explores the preventive effects of quinoa polysaccharides (QPS) on lipopolysaccharide (LPS)-induced systemic acute inflammation in mice and their mechanism of action. The findings revealed that QPS alleviated LPS-induced inflammation symptoms, enhanced the mice behavior score and their immune organ index, reduced pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) levels, elevated the expression level of tight junction proteins (ZO-1, MUC2). Additionally, the levels of superoxide dismutase (SOD), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) were improved via QPS administration. Further, our research suggested that QPS enhanced the diversity and abundance of gut microbiota compared to that of LPS mice, leading to an increase in the short-chain fatty acids in mice feces. Linear discriminant analysis (LDA) effect size (LEfSe) showed that QPS administration could lead to a range of gut biomarkers, promoting the enhancement of polysaccharide-metabolizing bacteria. The results of 16S rRNA sequencing indicated that QPS alleviates LPS-induced inflammation by enhancing the richness of beneficial bacteria such as Bacteroides and Lactobacillus. Linear discriminant analysis (LDA) effect size (LEfSe) showed that QPS administration could lead to a range of gut biomarkers, promoting the enhancement of polysaccharide-metabolizing bacteria. UPLC Q-TOF-MS was performed to analyze metabolites in the fecal samples. LPS administration significantly altered metabolite levels detected in mice feces in which some metabolites have decreased such as xanthosine and hypoxanthine while an increase in some metabolites in mice that received QPS, metabolomics analysis showed the beneficial effects of QPS primarily mediated via amino and bile acid-related metabolism pathways. Our research could offer the basis for further studies and applications of quinoa polysaccharides.PMID:40068754 | DOI:10.1016/j.ijbiomac.2025.141899

Cell. 2025 Mar 7:S0092-8674(25)00195-3. doi: 10.1016/j.cell.2025.02.010. Online ahead of print.ABSTRACTBifidobacteria represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest in bifidobacteria as a live biotic therapy, our understanding of colonization, host-microbe interactions, and the health-promoting effects of bifidobacteria is limited. To address these major knowledge gaps, we used a large-scale genetic approach to create a mutant fitness compendium in Bifidobacterium breve. First, we generated a high-density randomly barcoded transposon insertion pool and used it to determine fitness requirements during colonization of germ-free mice and chickens with multiple diets and in response to hundreds of in vitro perturbations. Second, to enable mechanistic investigation, we constructed an ordered collection of insertion strains covering 1,462 genes. We leveraged these tools to reveal community- and diet-specific requirements for colonization and to connect the production of immunomodulatory molecules to growth benefits. These resources will catalyze future investigations of this important beneficial microbe.PMID:40068681 | DOI:10.1016/j.cell.2025.02.010

Cancer Cell. 2025 Mar 10;43(3):361-379.e10. doi: 10.1016/j.ccell.2025.02.010.ABSTRACTThe mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of cancer patients and in tumor-bearing mice. The abscopal effects of ILDR depend on dosimetry (≥1 and ≤3 Gy) and on the metabolic and immune host-microbiota interaction at baseline allowing CD8+ T cell activation without exhaustion. Various strains of Christensenella minuta selectively boost the anti-cancer efficacy of ILDR and PD-L1 blockade, allowing emigration of intestinal PD-L1-expressing dendritic cells to tumor-draining lymph nodes. An interventional phase 2 study provides the proof-of-concept that ILDR can circumvent resistance to first- or second-line immunotherapy in cancer patients. Prospective clinical trials are warranted to define optimal dosimetry and indications for ILDR to maximize its therapeutic potential.PMID:40068595 | DOI:10.1016/j.ccell.2025.02.010

Poult Sci. 2025 Mar 4;104(4):104981. doi: 10.1016/j.psj.2025.104981. Online ahead of print.ABSTRACTThe accumulation of abdominal fat and the metabolic dysfunction-associated fatty liver disease (MAFLD) are prevalent problems in the poultry industry, and seriously compromise broiler health and reduce economic benefits. Echinocystic acid (EA), a natural product with anti-inflammatory and antioxidant effects, has been demonstrated to reduce abdominal fat deposition and improve intestinal inflammation in mice. However, it has not been reported in poultry research. In this study, we employed chicken hepatocytes (Leghorn male hepatoma cells, LMHs) to construct an oleic acid and palmitic acid (OA/PA)-induced MAFLD model in vitro and 60 male K90 chickens were induced MAFLD by a high-fat diet (HFD) to examine the impact of EA on liver-lipid metabolism and abdominal fat deposition. Moreover, metabolomic analysis, 16S rDNA gene sequencing, and transcriptomic profiling were performed to determine the mechanism of EA. The results showed that EA (10 μM) significantly reduced triglyceride (TG) and total cholesterol (TC) levels in vitro. Moreover, EA reduced abdominal fat deposition without affecting growth performance. EA significantly decreased TC, TG, and low-density lipoprotein-cholesterol (LDL-C) levels, and increased high-density lipoprotein-cholesterol (HDL-C) levels in the blood. Additionally, EA supplementation altered the composition of the intestinal microbiota, particularly by decreasing the ratio of Firmicutes to Bacteroidetes. Furthermore, liver metabolomics analysis revealed that EA increased the abundance of metabolites related to arginine metabolism and mitochondrial oxidation pathways, and these metabolites were predicted to be positively correlated with the gut genera enriched by EA. EA also altered the expression patterns of genes related to liver lipid metabolism and inflammation, particularly CYP7A1, CYP7B1, CYP3A5, and ACAT, which are enriched in the PPAR signaling pathway and steroid hormone metabolism. Moreover, correlation analysis revealed that there was a close correlation between differential gut microbiota, metabolites, and gene expression profiles. Collectively, the results indicated that EA may alleviate MAFLD by regulating steroid hormone metabolism and modulating the gut microbiota. EA may be a candidate feed additive to prevent abdominal fat deposition and MAFLD in the broiler industry.PMID:40068576 | DOI:10.1016/j.psj.2025.104981

Ecotoxicol Environ Saf. 2025 Mar 10;293:118024. doi: 10.1016/j.ecoenv.2025.118024. Online ahead of print.ABSTRACTBACKGROUND: Perfluorooctane sulfonates (PFOS) are persistent environmental pollutants linked to developmental toxicity, but the mechanisms remain unclear. This study investigates the metabolic changes induced by PFOS exposure during early embryonic development and integrates metabolomic, transcriptomic, and molecular docking analyses to explore underlying mechanisms.METHODS: Mouse embryoid bodies (mEBs) were exposed to PFOS for 2 days, 4 days and 6 days. Metabolomic profiling was conducted to identify differential metabolites. Transcriptomic data were integrated with metabolomics using Cytoscape to map metabolic pathway alterations. Molecular docking simulations were performed to assess PFOS binding to key enzymes.RESULTS: PFOS exposure resulted in significant alterations in lipid (Erucic acid, L-carnitine), amino acid (L-methionine, creatine, hippuric acid, and spermine), and nucleotide metabolism (e.g., hypoxanthine). Integrated transcriptomic and metabolomic analysis revealed disrupted pathways included SLC25A20 regulated L-carnitine metabolism. Molecular docking simulations indicated that PFOS binds to methionine synthase and hypoxanthine guanine phosphoribosyl transferase, potentially inhibiting their function and disrupting metabolic homeostasis for L-methionine and hypoxanthine during embryonic development.CONCLUSION: PFOS exposure disrupts key metabolic pathways critical for embryogenesis, including lipid, amino acid, and nucleotide metabolism. Molecular docking and transcriptomic integration highlight enzyme targeting as a potential mechanism of PFOS-induced developmental toxicity. These findings provide novel insights into the molecular and metabolic disruptions caused by PFOS, with implications for understanding its developmental toxicity.PMID:40068550 | DOI:10.1016/j.ecoenv.2025.118024

Comput Biol Med. 2025 Mar 10;189:109992. doi: 10.1016/j.compbiomed.2025.109992. Online ahead of print.ABSTRACTBACKGROUND: Coronary microvascular disease (CMVD), marked by dysfunction of the small coronary vessels, poses significant diagnostic challenges due to the complexity and high cost of current procedures like the index of microcirculatory resistance (IMR). This study aimed to identify metabolomic biomarkers from coronary artery samples to facilitate CMVD diagnosis using advanced bioinformatics techniques-specifically, random forest algorithms and generalized linear models (GLMs)-to develop more cost-effective blood-based diagnostics.METHODS: In this prospective study, 68 patients scheduled for coronary angiography and IMR assessment were enrolled. Plasma samples obtained from their coronary arteries were analyzed using untargeted metabolomics with liquid chromatography-mass spectrometry. Advanced bioinformatics methods were applied: random forest algorithms were utilized for feature selection to identify significant metabolites, and GLMs were constructed for predictive modeling. The diagnostic performance of the models was evaluated through receiver operating characteristic (ROC) curve analysis.RESULTS: The random forest analysis identified the top 10 metabolites that significantly contributed to the classification of CMVD. The GLM built using these metabolites demonstrated excellent diagnostic accuracy, achieving area under the ROC curve (AUC) values of 0.984 in the initial (discovery) cohort and 0.938 in the subsequent (validation) cohort. The use of mathematical modeling enhanced the robustness and interpretability of the biomarker selection process.CONCLUSIONS: Advanced bioinformatics techniques, including random forest algorithms and GLMs, effectively identified key metabolites associated with CMVD. While the collection of coronary artery blood samples is invasive due to the necessity of coronary angiography, this method offers a more practical and cost-effective alternative to IMR measurement, potentially improving the diagnostic approach for CMVD.PMID:40068493 | DOI:10.1016/j.compbiomed.2025.109992

Microbiol Res. 2025 Mar 7;296:128134. doi: 10.1016/j.micres.2025.128134. Online ahead of print.ABSTRACTThe metabolism of the crop rhizosphere affects microflora diversity and nutrient cycling. However, understanding rhizosphere metabolism in suitable crops within arid desert environments and its impact on microflora interactions remains limited. Through metagenomic and non-targeted metabolomic sequencing of rhizosphere soils from one uncultivated land and four vineyards with cropping years of 5, 10, 15 and 20 years, the critical importance of rhizosphere metabolites in maintaining bacterial and fungal diversity was elucidated. The results revealed that Nocardioides, Streptomyces, and Solirubrobacter were the relatively abundant bacterial genera in rhizosphere soils, while Rhizophagus, Glomus, and Pseudogymnoascus were the relatively abundant fungal genera. The composition of rhizosphere metabolic changed significantly during the continuous cropping of grapevines. Dimethylglycine, Formononetin, and Dehydroepiandrosterone were the most important metabolites. Enrichment analysis revealed significant involvement of metabolic pathways such as biosynthesis of amino acids, unsaturated fatty acids, and linoleic acid metabolism. Procrustes analysis highlighted stronger correlations between rhizosphere metabolites and bacterial community compared to those of fungal community. This suggests distinct responses of microflora to crop-released chemical elements across different soil habitats. Co-occurrence network analysis demonstrated complex associations between rhizosphere metabolites and soil microflora, the positive correlations between rhizosphere metabolites and microflora networks predominated over negative correlations. Partial least squares path model indicated that the effect of cropping years on rhizosphere metabolites was greater than that on bacterial microflora diversity. Futhermore, pH, total phosphorus, and alkali-hydrolyzed nitrogen were the key environmental factors affecting rhizosphere metabolites and microbial diversity. These results deepen our valuable insights into the complex biological processes that rhizosphere metabolites influence on microorganisms, and provide strong support for maintaining microbial diversity in farmland soils in arid regions.PMID:40068342 | DOI:10.1016/j.micres.2025.128134

Phytomedicine. 2025 Mar 10;140:156623. doi: 10.1016/j.phymed.2025.156623. Online ahead of print.ABSTRACTBACKGROUND: Stroke is a multifaceted physiological event linked to imbalances in gut microbiota and disruptions in metabolic pathways. Traditional Chinese medicines, leveraging the gut-brain axis, have been shown to significantly ameliorate ischemic stroke. However, the specific role and molecular mechanism of Shenqi granules (SQF) in enhancing the recovery from ischemic stroke remain to be elucidated.PURPOSE: This study aims to explore the therapeutic effects of SQF on rats with cerebral ischemia-reperfusion injury (CIRI) and its regulatory effects on the gut microbiota, providing a basis for the clinical rational use of drugs in ischemic stroke.METHODS: The study conducted a comprehensive biological assessment of SQF's role in improving CIRI at the whole-animal level. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) and network pharmacology analysis were used for component analysis and target prediction. Then, the therapeutic targets of SQF were further validated through molecular docking and molecular experiments. Finally, an integrated omics approach combining fecal untargeted metabolome and 16S rRNA sequencing was employed to state the anti-CIRI effects of SQF and its potential mechanisms.RESULTS: SQF alleviates cerebral infarct volume and improves cognitive functions in MCAO rats. Network pharmacology analysis shows 20 potential active ingredients of SQF could target 13 target proteins. Further employing WGCNA, our study identified four key targets of SQF in the treatment of ischemic stroke. Based on molecular docking and molecular experiments, SQF improves CIRI by activating NFE2L2/NRF2. Serum metabolomics analysis identified six metabolites related to the tryptophan and tyrosine metabolic pathways, which interact with NFE2L2/NRF2 protein. Fecal metabolome and microbiome reveal that SQF's protective effect on CIRI is linked to the tryptophan metabolism and tyrosine metabolism and gut microbiome modulation. In particular, metabolites related to tryptophan and tyrosine metabolism, such as kynurenic acid and dopamine, may exert their protective effects by interacting with NFE2L2/NRF2.CONCLUSION: This pioneering study unveils the therapeutic potential of SQF in addressing CIRI, highlighting the pivotal role of NFE2L2/NRF2 upregulation in its mechanism of action. Furthermore, SQF demonstrates its efficacy in restoring gut microbiota balance by modulating the metabolism of tryptophan and tyrosine in CIRI. By elucidating the intricate interplay among constituents, targets, metabolites, and gut microbiota, this research offers novel insights into the multifaceted mechanisms underlying SQF's therapeutic impact on CIRI.PMID:40068292 | DOI:10.1016/j.phymed.2025.156623

Clin Lab. 2025 Mar 1;71(3). doi: 10.7754/Clin.Lab.2024.240757.ABSTRACTBACKGROUND: Differential diagnosis of pleural effusions poses a considerable challenge in clinical practice. In this study, we explored biomarkers in pleural fluid for distinguishing tuberculosis, malignant, and parapneumonic pleural effusion patients.METHODS: A total of 166 patients with exudative pleural effusion were collected, including 86 patients with tuberculosis pleural effusion (TPE), 52 patients with malignant pleural effusion (MPE), and 28 patients with parapneumonic effusion (PE). Hydrogen nuclear magnetic resonance (1HNMR) based metabolomics and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) were employed to analyze the pleural fluid.RESULTS: There were significant differences in the levels of bile acid, leucine, citrulline, pyruvate, betaine, and taurine in the pleural effusion of the three groups (p < 0.05) by 1HNMR, indicating significant changes in amino acid metabolism among groups. Twelve amino acids in pleural effusion were further quantitatively determined by UPLC-MS. The results showed that arginine could be used to distinguish MPE from PE and TPE with the area under the ROC curve (AUC) value of 0.87, and lysine could distinguish PE from TPE with the AUC value of 0.74.CONCLUSIONS: Pleural fluid arginine could be used as a potential biomarker for distinguishing MPE from PE and TPE, and lysine could be used for distinguishing PE from TPE, which is worthy of further study.PMID:40066549 | DOI:10.7754/Clin.Lab.2024.240757

Burns Trauma. 2025 Mar 10;13:tkaf009. doi: 10.1093/burnst/tkaf009. eCollection 2025.ABSTRACTBACKGROUND: Diabetic wounds pose significant clinical challenges due to impaired healing processes, often resulting in chronic, nonhealing ulcers. Asiaticoside (AC), a natural triterpene derivative from Centella asiatica, has demonstrated notable anti-inflammatory and wound-healing properties. However, the synergistic effects of nitric oxide (NO)-a recognized promoter of wound healing-combined with AC in treating diabetic wounds remain inadequately explored.METHODS: Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was utilized to identify differential metabolites and dysregulated metabolic pathways associated with diabetic wounds. Molecular docking analyses were conducted to confirm the binding affinity of AC to key therapeutic targets. The effects of asiaticoside-nitric oxide hydrogel (ACNO) on gene and protein expression were evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. In vitro experiments using sarcoma (SRC) agonists and inhibitors were performed to investigate the impact of ACNO therapy on the expression of SRC, STAT3, and other proteins in HaCaT cells.RESULTS: Metabolomic profiling revealed that diabetic wounds in mice exhibited marked metabolic dysregulation, which was attenuated by ACNO treatment. Key metabolites modulated by ACNO included mandelic acid, lactic acid, and 3-hydroxyisovaleric acid. The primary metabolic pathways involved were methyl histidine metabolism and the malate-aspartate shuttle. Immunofluorescence staining confirmed that ACNO therapy enhanced angiogenesis, promoted cellular proliferation, and facilitated diabetic wound closure. RT-qPCR data demonstrated that ACNO regulated the transcription of critical genes (SRC, STAT3, EGFR, and VEGFA). Notably, ACNO attenuated SRC/STAT3 pathway activation while concurrently upregulating EGFR and VEGFA expression.CONCLUSIONS: These findings emphasize the therapeutic potential of ACNO hydrogel in diabetic wound healing through the modulation of metabolic pathways and the SRC/STAT3 signaling axis. By correlating altered metabolites with molecular targets, this study elucidates the pharmacodynamic foundation for ACNO's preclinical application and provides valuable insights into the development of targeted therapies for diabetic wound management.PMID:40066291 | PMC:PMC11891651 | DOI:10.1093/burnst/tkaf009

Front Microbiol. 2025 Feb 24;16:1480411. doi: 10.3389/fmicb.2025.1480411. eCollection 2025.ABSTRACTINTRODUCTION: Nus-dependent Mexican Escherichia coli phages (mEp) were previously isolated from clinical samples of human feces. Approximately 50% corresponded to non-lambdoid temperate phages integrating a single immunity group, namely immunity I (mEpimmI), and these were as prevalent as the lambdoid phages identified in such collection.METHODS: In this work, we present the structural and functional characterization of six representative mEpimmI phages (mEp010, mEp013, mEp021, mEp044, mEp515, and mEp554). In addition, we searched for homologous phages and prophages in the GenBank sequence database, and performed extensive phylogenetic analyses on the compiled genomes.RESULTS: A biological feature-based characterization of these phages was carried out, focusing on proteins relevant to phage biological activities. This included mass spectrometry analysis of mEp021 virion structural proteins, and a series of infection assays to characterize the function of the main repressor protein and the lipoproteins associated with superinfection-exclusion; to identify the main host receptor proteins recognized by these phages and the prophage insertion sites within the host genome, which were associated with specific integrase sequence-types present in the viral genomes. Further, we compiled 42 complete homologous genomes corresponding to 38 prophages from E. coli strains and 4 phages from metagenomes, displaying a wide geographical distribution. Intergenomic distance analyses revealed that these phages differ from previously established phage clades, and whole-proteome similarity analyses yielded a cohesive and monophyletic branch, when compared to >5,600 phages with dsDNA genomes.DISCUSSION: According to current taxonomic criteria, our results are consistent with a novel family demarcation, and the studied genomes correspond to 9 genera and 45 distinct species. Further, we identified 50 core genes displaying high synteny among the mEpimmI genomes, and these genes were found arranged in functional clusters. Furthermore, a biological feature-based characterization of these phages was carried out, with experiments focusing on proteins relevant to phage biological activities, revealing common traits as well as diversity within the group. With the integration of all these experimental and bioinformatics findings, our results indicate that the mEpimmI phages constitute a novel branch of Caudoviricetes distinct to other known siphovirus, contributing to the current knowledge on the diversity of phages infecting Escherichia coli.PMID:40066275 | PMC:PMC11893012 | DOI:10.3389/fmicb.2025.1480411

Front Neurosci. 2025 Feb 24;19:1542016. doi: 10.3389/fnins.2025.1542016. eCollection 2025.ABSTRACTBACKGROUND: Circadian rhythms and sleep patterns are important regulators of metabolic health. During Ramadan intermittent fasting (RIF), the sleep-wake cycles are often disrupted, which can affect physical activity (PA) and related metabolic responses. Limited knowledge is available on how sleep disruption influences PA in the general population during RIF. This pilot study aimed to examine the metabolic responses to moderate PA under normal and disrupted sleep patterns during RIF.METHODS: A pilot study was conducted on 12 participants comprising of individuals with normal (n = 5) and disrupted sleep patterns (n = 7). Blood samples were collected, and measurements of clinical traits, cytokines, homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic profiles were performed before and after intervention. Orthogonal partial least square - discriminant analysis (OPLS-DA) and linear regressions were performed to assess metabolic responses to PA during RIF under different patterns.RESULTS AND CONCLUSION: Fasting participants with normal sleep patterns exhibited lower HOMA-IR (β = -0.416, p = 0.047) in response to PA compared to those with disrupted sleep. Additionally, they demonstrated more efficient lipid utilization during PA, characterized by reduced diacylglycerol levels, which could enhance insulin sensitivity and lower the risk of type 2 diabetes. In contrast, fasting participants with disrupted sleep patterns experienced metabolic stress, marked by significant depletion of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and plasmalogens in response to PA. These changes were associated with increased inflammation and oxidative stress, potentially leading to metabolic dysregulation.PMID:40066156 | PMC:PMC11891360 | DOI:10.3389/fnins.2025.1542016

Front Cell Infect Microbiol. 2025 Feb 24;15:1488874. doi: 10.3389/fcimb.2025.1488874. eCollection 2025.ABSTRACTSignificant changes in gut microbial composition are associated with chronic liver disease. Using preclinical models, it has been demonstrated that ethanol/alcohol-induced liver disease is transmissible through fecal microbiota transplantation (FMT). So, the survival rate of people with severe alcoholic hepatitis got better, which suggests that changes in the makeup and function of gut microbiota play a role in metabolic liver disease. The leaky intestinal barrier plays a major role in influencing metabolic-related liver disease development through the gut microbiota. As a result, viable bacteria and microbial products can be transported to the liver, causing inflammation, contributing to hepatocyte death, and causing the fibrotic response. As metabolic-related liver disease starts and gets worse, gut dysbiosis is linked to changes in the immune system, the bile acid composition, and the metabolic function of the microbiota in the gut. Metabolic-related liver disease, as well as its self-perpetuation, will be demonstrated using data from preclinical and human studies. Further, we summarize how untargeted treatment approaches affect the gut microbiota in metabolic-related liver disease, including dietary changes, probiotics, antibiotics, and FMT. It discusses how targeted therapies can improve liver disease in various areas. These approaches may improve metabolic-related liver disease treatment options.PMID:40066068 | PMC:PMC11891185 | DOI:10.3389/fcimb.2025.1488874

Biotechnol J. 2025 Mar;20(3):e202400624. doi: 10.1002/biot.202400624.ABSTRACTBiopharmaceuticals are medical compounds derived from biological sources and are often manufactured by living cells, primarily Chinese hamster ovary (CHO) cells. CHO cells display variation among cell clones, leading to growth and productivity differences that influence the product's quantity and quality. The biological and environmental factors behind these differences are not fully understood. To identify metabolites with a consistent relationship to productivity or cell death over time, we analyzed the extracellular metabolome of 11 CHO clones with different growth and productivity characteristics over 14 days. However, in bioreactor processes, metabolic profiles and process variables are both strongly time-dependent, confounding the metabolite-process variable relationship. To address this, we customized an existing hierarchical approach for handling time dependency to highlight metabolites with a consistent correlation to a process variable over a selected timeframe. We benchmarked this new method against conventional orthogonal partial least squares (OPLS) models. Our hierarchical method highlighted several metabolites consistently related to productivity or cell death that the conventional method missed. These metabolites were biologically relevant; most were known already, but some that had not been reported in CHO literature before, such as 3-methoxytyrosine and succinyladenosine, had ties to cell death in studies with other cell types. The metabolites showed an inverse relationship with the response variables: those positively correlated with productivity were typically negatively correlated with the death rate, or vice versa. For both productivity and cell death, the citrate cycle and adjacent pathways (pyruvate, glyoxylate, pantothenate) were among the most important. In summary, we have proposed a new method to analyze time-dependent omics data in bioprocess production. This approach allowed us to identify metabolites tied to cell death and productivity that were not detected with traditional models.PMID:40065671 | DOI:10.1002/biot.202400624

Plant Cell Environ. 2025 Mar 10. doi: 10.1111/pce.15457. Online ahead of print.ABSTRACTPot size is a critical factor in plant growth experiments, influencing root architecture, nutrient uptake, and overall plant development as well as sensing of stress. In controlled environments, variation in pot size can impact phenotypic and molecular outcomes and may bias experimental results. Here, we investigated how pot size affects the root system architecture and molecular responses of two barley genotypes, the landrace BERE and the modern elite CONCERTO, through assessment of shoot and root traits and by using X-ray computed tomography complemented by transcriptomic and metabolomic analyses. The two genotypes showed distinctly different adaptations to changes in pot size. The landrace showed greater stability and adaptability with consistent root traits and enhanced accumulation of osmoprotectant metabolites across different pot sizes with respect to CONCERTO. Conversely, the elite line was more sensitive to pot size variations, particularly showing altered root architecture and transcriptomic responses. Overall, this study highlights the importance of selecting an appropriate pot size for plant growth experiments, particularly when focused on root traits, and highlights the importance of considering the physiological and molecular changes due to growth environment choice in experimental design in barley.PMID:40065576 | DOI:10.1111/pce.15457

Int J Cancer. 2025 Mar 10. doi: 10.1002/ijc.35392. Online ahead of print.ABSTRACTGastric microbiota and metabolites may interact and play collaborative roles in the carcinogenesis process. This study aims to investigate differential metabolites and microbes, as well as the possible roles of microbe-metabolite interactions in gastric cancer (GC) development. Targeted metabolomics assays and 16S rRNA sequencing were performed to compare metabolic and microbial profiles in gastric tissues from subjects with superficial gastritis/chronic atrophic gastritis (SG/CAG), intestinal metaplasia/low-grade intraepithelial neoplasia (IM/LGIN) and GC. Significant differences were found in metabolic and microbial profiles between the GC and SG/CAG or IM/LGIN groups, respectively (all p < .05). By comparing GC with the other lesions, 69 differential metabolites mainly comprised triglycerides and phosphatidylcholines, and 21 differential microbes included Peptostreptococcus, Lactobacillus, Dialister, Helicobacter pylori, and Streptococcus anginosus (all p < .05). The altered metabolites and microbes in GC were both significantly enriched in the glycerophospholipid metabolism pathway, in which the predicted down-regulation of phospholipase C (plc) and up-regulation of 1-acyl-sn-glycerol-3-phosphate acyltransferase (plsC) by microbiota may affect phosphatidylcholine hydrolysis and triglyceride biosynthesis modules. More and stronger microbe-metabolite correlations in GC compared to the other lesion group further supported the potential microbial regulations to the important metabolites in gastric carcinogenesis, such as Lactobacillus and phosphatidylcholines (.32 ≤ r ≤ .57, all p < .05), Peptostreptococcus (.36 ≤ r ≤ .60, all p < .05) or Dialister (.36 ≤ r ≤ .62, all p < .05) and triglycerides. We simultaneously identified differential metabolites and microbes and their altered correlations between GC and gastric lesions. The main GC-associated phosphatidylcholines and triglycerides may be affected by gastric microbes, which provides new perspectives on the microbiota-metabolite interactions during the development of GC.PMID:40065492 | DOI:10.1002/ijc.35392