PubMed

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

Environ Microbiol. 2025 Mar;27(3):e70057. doi: 10.1111/1462-2920.70057.ABSTRACTThe specific association of the potentially plant-pathogenic Pseudomonas syringae with Peltigera lichens raises questions about the factors driving this host specificity. To explore this, the metabolic profile of seven lichen species belonging to three genera (Cladonia, Peltigera and Stereocaulon) was analysed using LC-MSMS. In addition, we assessed the growth of P. syringae strains in media supplemented with extracts from each lichen species. This revealed that Peltigera exhibits lower metabolite richness compared to other genera, but shows a higher chemical investment in specific compounds. Growth kinetics showed comparable P. syringae growth across lichen-supplemented media, except for Cladonia arbuscula and Cladonia sp., where the former exhibited lower growth rates. Inhibition assays with lichen extracts showed no inhibition of P. syringae. The lichen metabolome is predominantly composed of lipids and organic acids. Furthermore, specific compounds, such as aminoglycosides, may facilitate P. syringae presence in Peltigera by inhibiting Bacillus subtilis and other antagonists. In addition, compounds absent in Peltigera, like anthracene, might serve as a carbon source inhibitor like Bacillus velezensis.PMID:40065488 | DOI:10.1111/1462-2920.70057

Vet Res. 2025 Mar 11;56(1):55. doi: 10.1186/s13567-025-01478-z.ABSTRACTCystic echinococcosis (CE) is a parasitic disease caused by the larval stage of Echinococcus granulosus, and the immunosuppressive microenvironment exacerbates disease progression. Ghrelin, a peptide hormone, plays a role in modulating immune inflammation and may influence the progression of E. granulosus infection through its receptor, GHSR (growth hormone secretagogue receptor). However, whether GHSR downregulation can inhibit E. granulosus infection remains unclear. In this study, we extracted liver tissues from E. granulosus-infected mice and those treated with the GHSR antagonist [D-Lys3]-GHRP-6. Proteomic analysis revealed 341 differentially expressed proteins, of which 185 were upregulated and 156 were downregulated. Metabolomic sequencing revealed 101 differentially expressed metabolites, including 62 upregulated and 39 downregulated metabolites. KEGG pathway enrichment analysis of both proteomic and metabolomic data revealed seven key signalling pathways, 11 key proteins, and 26 key metabolites that interact through metabolic and organic system networks. Next, we examined the disease progression of E. granulosus infection in GHSR-knockout mice. Compared with the E. granulosus (Eg) group, the GHSR-KO group presented a significant reduction in the number of liver infection foci. The serum and liver ghrelin levels were significantly greater in the E. granulosus group than in the control group, along with increased secretion of proinflammatory cytokines (IL-2 and IFN-γ) and decreased secretion of anti-inflammatory cytokines (IL-4 and IL-10). In contrast, the GHSR-KO group presented significantly lower ghrelin levels in both the serum and liver, with reduced proinflammatory cytokine secretion and increased anti-inflammatory cytokine secretion, similar to those of the control group. Furthermore, ghrelin and inflammation-related factors, including MyD88, NF-κB p65, iNOS, and Arg-1, exhibited coordinated expression changes in liver lesions and surrounding areas. These findings suggest that GHSR gene knockout can ameliorate the progression of liver E. granulosus infection and associated liver inflammation.PMID:40065480 | DOI:10.1186/s13567-025-01478-z

BMC Immunol. 2025 Mar 10;26(1):18. doi: 10.1186/s12865-025-00700-z.ABSTRACTBACKGROUND: Inflammatory bowel disease (IBD) has become a global healthcare issue, with its incidence continuing to rise, but currently there is no complete cure. Xylitol is a widely used sweetener in various foods and beverages, but there is limited research on the effects of xylitol on IBD symptoms.AIM: Study on the effect of oral xylitol in improving intestinal inflammation and damage in IBD mice, further explore the mechanism of xylitol in alleviating IBD symptoms using intestinal microbiota and non-targeted metabolomics techniques.METHODS: An IBD mouse model was induced using sodium dextran sulfate (DSS). After 30 days of oral administration of xylitol, we assessed the disease activity index (DAI) scores of mice in each group. The expression levels of inflammatory factors in the colon tissues were measured using qPCR. Additionally, we examined the damage to the intestinal mucosa and tight junction structures through HE staining and immunohistochemical staining. Finally, the alterations in the gut microbiota of the mice were analyzed using 16S rDNA sequencing technology.The production of three main short-chain fatty acids (SCFAs, including acetate, propionic acid and butyric acid) in feces and the changes of serum metabolomics were measured by non-targeted metabolomics techniques.RESULTS: The findings indicated that xylitol effectively mitigated weight loss and improved the DAI score in mice with IBD. Moreover, xylitol reduced the expressions of Caspase-1, IL-1β, and TNF-α in the colon tissue of the mice, and increased the expressions of ZO-1 and occludin in intestinal mucosal. Xylitol could enhance the variety of intestinal bacteria in IBD mice and influenced the abundance of different bacterial species. Additionally, metabolomic analysis revealed that oral xylitol increased the levels of three main SCFAs in the feces of IBD mice, while also impacting serum metabolites.CONCLUSIONS: Our findings suggest that xylitol can help improve IBD symptoms. Xylitol can improve the intestinal flora of IBD mice and increase the production of SCFAs to play an anti-inflammatory role and protect the mucosal tight junction barrier. These discoveries present a fresh prophylactic treatment of IBD.CLINICAL TRIAL NUMBER: Not applicable.PMID:40065221 | DOI:10.1186/s12865-025-00700-z

EMBO Mol Med. 2025 Mar 10. doi: 10.1038/s44321-025-00202-w. Online ahead of print.ABSTRACTHost-microbiome communication is frequently perturbed in gut pathologies due to microbiome dysbiosis, leading to altered production of bacterial metabolites. Among these, 7α-dehydroxylated bile acids are notably diminished in inflammatory bowel disease patients. Herein, we investigated whether restoration of 7α-dehydroxylated bile acids levels by Clostridium scindens, a human-derived 7α-dehydroxylating bacterium, can reestablish intestinal epithelium homeostasis following colon injury. Gnotobiotic and conventional mice were subjected to chemically-induced experimental colitis following administration of Clostridium scindens. Colonization enhanced the production of 7α-dehydroxylated bile acids and conferred prophylactic and therapeutic protection against colon injury through epithelial regeneration and specification. Computational analysis of human datasets confirmed defects in intestinal cell renewal and differentiation in ulcerative colitis patients while expression of genes involved in those pathways showed a robust positive correlation with 7α-dehydroxylated bile acid levels. Clostridium scindens administration could therefore be a promising biotherapeutic strategy to foster mucosal healing following colon injury by restoring bile acid homeostasis.PMID:40065134 | DOI:10.1038/s44321-025-00202-w

Sci Rep. 2025 Mar 10;15(1):8247. doi: 10.1038/s41598-025-90361-0.ABSTRACTMicrobial fuel cell (MFC) can convert the chemical energy of organic matter in wastewater into electrical energy with high degradation efficiency. In this study, a type of specialized microorganism, Pseudomonas aeruginosa, was screened and added to an MFC to promote the degradation of wastewater generated during the production of cytidine acid while improving the performance of the MFC. The MFC achieved a maximum voltage of 57.7 ± 4.4 mV and a maximum power density of 1.9 ± 0.1 mW/m2; moreover, the degradation efficiencies of chemical oxygen demand (COD), total phosphorus (TP), and phosphate reached 76.3 ± 2.8%, 80.3 ± 3.3%, and 85.3 ± 3.5%, respectively. Gas chromatography-mass spectrometry (GC-MS) and metabolomics analysis revealed that Pseudomonas aeruginosa could effectively degrade organic matter in wastewater. Additionally, the metabolic pathways involved may have been pyrimidine metabolism, arginine and proline metabolism, and taurine and hypotaurine metabolism.PMID:40065049 | DOI:10.1038/s41598-025-90361-0

World J Microbiol Biotechnol. 2025 Mar 11;41(3):101. doi: 10.1007/s11274-025-04298-7.ABSTRACTNatural products (NPs) of microbial origin are highly valued for their diverse bioactive properties. Among bacteria, Streptomyces stands out as a prolific source of NPs with applications in medicine and agriculture. Recent advances in metabolomics, and bioinformatics as well as the abundance of genomic data have revolutionized the study of NPs, enabling the rapid connection of biosynthetic pathways and metabolites. However, discovering novel compounds from large pools of genomes and strains is cumbersome. Metabolo-genomics approaches are promising strategies that can save time and resources at initial stages of the natural product discovery pipeline by rapidly linking molecules and their biosynthetic genes. Here, we present genomic characterization and metabolomic profiling of Streptomyces sp. KL110A, a strain isolated from the rainforest soils of Calakmul, Campeche in Mexico. Using genome mining tools and LC-MS/MS metabolomics, we identified and characterized known biosynthetic gene clusters (BGCs) and proposed a biosynthetic mechanism for the biosynthesis of the benz(a)anthraquinone tetrangulol. Our findings underscore the relevance of integrating genomic and metabolomic approaches in elucidating novel biosynthetic pathways, positively contributing to the field of natural product research.PMID:40064729 | DOI:10.1007/s11274-025-04298-7

Metabolomics. 2025 Mar 10;21(2):39. doi: 10.1007/s11306-025-02226-2.ABSTRACTINTRODUCTION: Metabolic steatotic liver disease (MASLD) can progress to hepatocellular carcinoma (HCC). 25% of MASLD-HCCs occur in the absence of fibrosis.OBJECTIVES: This study aimed to explore lipid metabolic pathways through "omics" and to identify biomarkers of MASLD-HCC based on the degree of fibrosis.METHODS: Our cohort included 79 pairs of MASLD-HCC tumor tissues (TT) and adjacent non-tumor human liver tissues (NTT), which were divided into two groups according to fibrosis degree (F0F2 n = 45 and F3F4 n = 34). Lipidomic analysis (n = 52) using liquid chromatography high-resolution mass spectrometry (LC-HRMS/MS) and gene expression analysis (n = 79) using RT-qPCR were performed. For each group, TT was compared with NTT. Five healthy liver tissues were used as calibrators in gene expression analysis.RESULTS: Using LC-HRMS/MS, 130 lipids were putatively annotated, 30 of which showed a significant difference between TT and NTT. In MASLD-HCC-F0F2, ceramide levels decreased. While sphingomyelin, most phosphatidylcholine and phosphatidylethanolamine species were increased. In contrast, in MASLD-HCC-F3F4, most lipid contents decreased. Based on lipidomic data, a panel of 18 genes related to lipid metabolism was analyzed. The expression of six genes, ACAT2, DGAT2, ACOX1, CHKA, PLD1, and PLD2, was exclusively upregulated in MASLD-HCC-F0F2. Taken together, these data support the existence of two MASLD-HCC lipid metabolic phenotypes, according to the degree of fibrosis.CONCLUSION: In conclusion, our results allow: (1) discriminate two phenotypes of MASLD-HCC according to fibrosis level; (2) propose PLD as a potential drug target for MASLD-HCC-F0F2 patients, and suggest that PLD inhibitor could be evaluated in combination with immunotherapy treatment.PMID:40064725 | DOI:10.1007/s11306-025-02226-2

Anal Bioanal Chem. 2025 Mar 10. doi: 10.1007/s00216-025-05818-y. Online ahead of print.ABSTRACTHigh-resolution mass spectrometers, particularly when paired with liquid chromatography, are the instrument of choice for untargeted metabolomics approaches. Instruments, such as the Orbitrap, offer high sensitivity, selectivity, and exceptional mass accuracy, though they pose certain technical challenges, complicating absolute and comparative quantification. Consequently, method validation is crucial to ensure reliable results, as untargeted metabolomics approaches require the detection and quantification of a large number of metabolites in a broad dynamic range. Methods can be assessed using performance characteristics like accuracy and linearity to ensure analytical reliability. This study evaluates the suitability of untargeted metabolomics methods for discovery-based investigations. A stable isotope-assisted strategy was used with wheat extracts analyzed by a Q Exactive HF Orbitrap. Results showed that 70% of all detected 1327 metabolites displayed non-linear effects in at least one of the nine dilution levels employed. However, when considering fewer levels, 47% of all metabolites demonstrated linear behavior in at least four levels (i.e., a difference factor of 8). Moreover, the analysis further suggests that the observed abundances in less concentrated samples and those outside the linear range were mostly overestimated compared to expected abundances, but hardly ever underestimated. Consequently, during statistical analysis, which is an important step in prioritizing detected metabolites and correlating them with the biological hypothesis, the number of false-positives was not inflated, but the number of false-negatives might be increased. Generally, (non-)linear behavior did not correlate with specific compound classes or polarity, suggesting non-linearity is not easily predictable based on chemical structures.PMID:40064673 | DOI:10.1007/s00216-025-05818-y

J Agric Food Chem. 2025 Mar 10. doi: 10.1021/acs.jafc.4c08012. Online ahead of print.ABSTRACTMaize is a globally important crop. Roots are the main part of maize and are mainly used for soil improvement and for maintaining crop growth as agricultural waste. Their application scope is relatively small. It is very important to analyze the components in maize roots in order to increase their resource utilization and reduce the burden of waste disposal. Metabolomics shows that maize roots contain various bioactive components, such as alkaloids, phenolic acids, flavonoids, etc. Therefore, this study explores the potential pharmacological effects of maize root metabolites under drought stress from the perspective of metabolomics combined with network pharmacology. The crude extraction of betaine, a metabolite in maize roots under drought stress, was conducted, and the anti-inflammatory and antioxidant effects of the crude extract were evaluated. The experimental results of DPPH, Fenton, etc. indicate that the crude extract of betaine from maize roots has certain anti-inflammatory and antioxidant effects, which provides a basis for its potential applications in the fields of medicine and food. The research on extracting medicinal active substances such as betaine from maize roots as agricultural waste not only has economic and environmental advantages but also has important significance in promoting technological progress and public health.PMID:40064553 | DOI:10.1021/acs.jafc.4c08012

J Adv Res. 2025 Mar 8:S2090-1232(25)00137-7. doi: 10.1016/j.jare.2025.02.039. Online ahead of print.ABSTRACTINTRODUCTION: Traditionally, the mechanism of dark tea quality formation has centered on microorganisms, with quality regulated by manipulating microorganisms and their fermentation environment. Nevertheless, raw teas, the natural selective medium of microbial community, was completely ignored in the formation of dark tea unique flavors.OBJECTIVES: This study aims to uncover the previously unappreciated interactions between raw tea and microorganisms, demonstrating the significant role of raw tea in the formation of dark tea quality.METHODS: Sun-dried raw tea (SDT), baked raw tea (BT), and pan-fried raw tea (PFT) were pile fermented. Chemical profiles, microbial communities, and sensory qualities were assessed by metabolomics, high-throughput sequencing, and sensory evaluation, with correlation and multiple factor analyses used to explore their relationships.RESULTS: Compared to PFT and BT, SDT had 18 % lower flavonoid content and 26 % lower catechin content, which favored dominant Agathobacter and Wickerhamomyces. Wickerhamomyces contributed to flower aroma by producing alcohols, esters and terpenes, while Agathobacter amplified acid production. The distinctive dominant bacterium Acidovorax in BT was positively correlated with alcohols and hydrocarbons, with Pearson's r > 0.6, resulting in a 47 % increase in volatile alcohol level, enhancing the fresh and refreshing attributes. A 70-80 % increase in iron concentration in PFT compared to SDT and BT resulted in the predominance of Geobacter, which exhibited a negative correlation with aldehydes. The presence of distinctive bacteria, Streptococcus and Ligilactobacillus, in PFT led to a significant rise in volatile acid content, increasing from 5 % to 25 %.CONCLUSION: The chemical profiles of raw tea could reshape local microbiota, which then drives unique qualities of dark tea. This indicates dark tea quality is not passively shaped by the environmental microorganisms, but actively screened by raw tea chemistry. This study paves the way for targeted manipulation of raw tea chemical profiles to achieve desired dark tea flavor characteristics.PMID:40064439 | DOI:10.1016/j.jare.2025.02.039