PubMed
Omics approaches to investigate pre-symbiotic responses of the mycorrhizal fungus Tulasnella sp. SV6 to the orchid host Serapias vomeracea
Mycorrhiza. 2025 Apr 2;35(2):26. doi: 10.1007/s00572-025-01188-6.ABSTRACTLike other plant-microbe symbioses, the establishment of orchid mycorrhiza (ORM) is likely to require specific communication and metabolic adjustments between the two partners. However, while modulation of plant and fungal metabolism has been investigated in fully established mycorrhizal tissues, the molecular changes occurring during the pre-symbiotic stages of the interaction remain largely unexplored in ORM. In this study, we investigated the pre-symbiotic responses of the ORM fungus Tulasnella sp. SV6 to plantlets of the orchid host Serapias vomeracea in a dual in vitro cultivation system. The fungal mycelium was harvested prior to physical contact with the orchid roots and the fungal transcriptome and metabolome were analyzed using RNA-seq and untargeted metabolomics approaches. The results revealed distinct transcriptomic and metabolomic remodelling of the ORM fungus in the presence of orchid plantlets, as compared to the free-living condition. The ORM fungus responds to the presence of the host plant with a significant up-regulation of genes associated with protein synthesis, amino acid and lipid biosynthesis, indicating increased metabolic activity. Metabolomic analysis supported the RNA-seq data, showing increased levels of amino acids and phospholipids, suggesting a remodelling of cell structure and signalling during the pre-symbiotic interaction. In addition, we identified an increase of transcripts of a small secreted protein that may play a role in early symbiotic signalling. Taken together, our results suggest that Tulasnella sp. SV6 may perceive information from orchid roots, leading to a readjustment of its transcriptomic and metabolomic profiles.PMID:40172721 | DOI:10.1007/s00572-025-01188-6
A comparative study of data-independent acquisition and data-dependent acquisition in liquid chromatography-mass spectrometry-based untargeted metabolomics analysis of Panax genus sample
Anal Bioanal Chem. 2025 Apr 2. doi: 10.1007/s00216-025-05861-9. Online ahead of print.ABSTRACTData-independent acquisition (DIA) and data-dependent acquisition (DDA) are frequently employed in the execution of tandem mass spectrometry (MS2) analyses. This study explored the application of DIA (MSe) and DDA (fast-DDA) in liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics using Panax genus samples. MSe provided comprehensive sample information, extracting more ion peaks with better peak shape and increased scan points compared to fast-DDA. Features from MSe data are four times more than those from fast-DDA data. Fast-DDA, however, delivered high-quality MS2 data, enhancing compound annotation via the GNPS web tool. Database matches with fast-DDA data were nearly 35 times greater than those using MSe data. Therefore, combining MSe and fast-DDA can improve data analysis and metabolite annotation. An improved workflow integrating DIA and DDA was proposed, requiring additional QC sample injections for DDA analysis but eliminating the need for sample reprocessing and re-analysis, thus saving time and resources. The established workflow was applied to the Panax genus samples analysis to confirm its applicability. This study offers a deeper understanding of DIA and DDA, guiding the selection of data acquisition strategies for LC-MS-based untargeted metabolomics.PMID:40172670 | DOI:10.1007/s00216-025-05861-9
Effects of combined prebiotic fiber supplementation and weight loss counseling in adults with metabolic dysfunction-associated steatotic liver disease: a randomized controlled trial
Eur J Nutr. 2025 Apr 2;64(4):144. doi: 10.1007/s00394-025-03660-7.ABSTRACTPURPOSE: Our aim was to examine the effects of combined prebiotic fiber supplementation and weight loss counseling on liver fat, body composition, subjective appetite, serum metabolomics, and intestinal microbiota in adults with MASLD.METHODS: In a double blind, placebo-controlled trial, adult participants aged 18-70 years old with MASLD were randomized to receive prebiotic (oligofructose-enriched inulin, 16 g/day; n = 22) or isocaloric placebo (maltodextrin; n = 20) for 24 weeks alongside weight loss counseling from a registered dietitian. Primary outcomes were change in intrahepatic fat % (IHF%) and hepatic injury from baseline to 24 weeks. Secondary outcomes included body composition, subjective appetite, serum lipids and cytokines, fecal microbiota, and serum metabolomics.RESULTS: At baseline, participants had IHF of 14.4 ± 8.4%. The change in IHF from baseline to 24 weeks did not differ between prebiotic and placebo. Prebiotic participants had a greater decrease (p = 0.029) in percent trunk fat compared to placebo. Compared to placebo, prebiotic significantly decreased desire to eat and hunger ratings over the course of the intervention. Fecal microbiota analysis showed a significant increase in Bifidobacterium abundance with prebiotic. A pathway analysis based on untargeted serum metabolomics revealed a downregulation of taurine and hypotaurine metabolism in the placebo group which was conserved in the prebiotic group.CONCLUSION: Adding prebiotic fiber supplementation to weight loss counseling for adults with MASLD enhanced reductions in trunk fat and had a beneficial effect on subjective appetite compared to placebo. Improvements in fecal microbial profile and taurine metabolism revealed specific beneficial effects of prebiotics in the management of MASLD.CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov/study/NCT02568605.PMID:40172664 | DOI:10.1007/s00394-025-03660-7
Advances in Tandem Mass Spectrometry Imaging for Next-Generation Spatial Metabolomics
Anal Chem. 2025 Apr 2. doi: 10.1021/acs.analchem.5c00157. Online ahead of print.ABSTRACTSpatial metabolomics based on mass spectrometry imaging (MSI) is a promising approach for fundamental biological research and disease biomarker discovery. It simultaneously reveals the spatial distributions of hundreds of metabolites across tissue sections. While previous MSI experiments predominantly rely on high-resolution mass analysis for metabolite annotation, the high specificity in resolving molecular structures is essential to distinguish isomers or isobars to obtain ultimate identities of the metabolites. This is also critical for correlating their biological functions with spatial distribution patterns. Tandem mass spectrometry (MS/MS) is effectively used to obtain molecular structural information and has been integrated into MSI for spatial mapping of structurally distinct biomolecules, though typically with low coverage. The main technical challenge in achieving high-coverage, high-structure-resolving spatial mapping of biomolecules lies in the limited amount of sample available from each tissue pixel in conventional MS/MS analysis, which restricts the number of MS/MS scans that can be conducted on the metabolite precursors of interest. In this Perspective, we highlight recent developments in advanced MS/MS imaging strategies aimed at achieving high-coverage spatial metabolomics.PMID:40172484 | DOI:10.1021/acs.analchem.5c00157
Metabolic adaptability and nutrient scavenging in <em>Toxoplasma gondii</em>: insights from ingestion pathway-deficient mutants
mSphere. 2025 Apr 2:e0101124. doi: 10.1128/msphere.01011-24. Online ahead of print.ABSTRACTThe obligate intracellular parasite Toxoplasma gondii replicates within a specialized compartment called the parasitophorous vacuole (PV). Recent work showed that despite living within a PV, Toxoplasma endocytoses proteins from the cytosol of infected host cells via a so-called ingestion pathway. The ingestion pathway is initiated by dense granule protein GRA14, which binds host endosomal sorting complex required for transport (ESCRT) machinery to bud vesicles into the lumen of the PV. The protein-containing vesicles are internalized by the parasite and trafficked to the plant vacuole-like compartment (PLVAC), where cathepsin protease L (CPL) degrades the cargo, and the chloroquine resistance transporter (CRT) exports the resulting peptides and amino acids to the parasite cytosol. However, although the ingestion pathway was proposed to be a conduit for nutrients, there is limited evidence for this hypothesis. We reasoned that if Toxoplasma uses the ingestion pathway to acquire nutrients, then parasites lacking GRA14, CPL, or CRT should rely more on biosynthetic pathways or alternative scavenging pathways. To explore this, we conducted a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen in wild-type (WT) parasites and Δgra14, Δcpl, and Δcrt mutants to identify genes that become more fitness conferring in ingestion-deficient parasites. Our screen revealed a significant overlap of genes that potentially become more fitness conferring in the ingestion mutants compared to WT. Pathway analysis indicated that Δcpl and Δcrt mutants relied more on pyrimidine biosynthesis, fatty acid biosynthesis, tricarboxylic acid (TCA) cycle, and lysine degradation. Bulk metabolomic analysis showed reduced levels of glycolytic intermediates and amino acids in the ingestion mutants compared to WT, highlighting the pathway's potential role in host resource scavenging. Interestingly, Δcpl and Δcrt showed an exacerbated growth defect when cultured in amino acid-depleted media, suggesting that disrupting proteolysis or the export of proteolytic products from the PLVAC affects parasite survival during nutrient scarcity.IMPORTANCE: Toxoplasma gondii is an obligate intracellular pathogen that infects virtually any nucleated cell in most warm-blooded animals. Infections are asymptomatic in most cases, but people with weakened immunity can experience severe disease. For the parasite to replicate within the host, it must efficiently acquire essential nutrients, especially as it is unable to make several key metabolites. Understanding the mechanisms by which Toxoplasma scavenges nutrients from the host is crucial for identifying potential therapeutic targets. Our study suggests that the ingestion pathway contributes to sustaining parasite metabolites and parasite replication under amino acid-limiting conditions. This work advances our understanding of the metabolic adaptability of Toxoplasma.PMID:40172222 | DOI:10.1128/msphere.01011-24
Integrative metagenomics and metabolomics reveal age-associated gut microbiota and metabolite alterations in a hamster model of COVID-19
Gut Microbes. 2025 Dec;17(1):2486511. doi: 10.1080/19490976.2025.2486511. Epub 2025 Apr 2.ABSTRACTAging is a key contributor of morbidity and mortality during acute viral pneumonia. The potential role of age-associated dysbiosis on disease outcomes is still elusive. In the current study, we used high-resolution shotgun metagenomics and targeted metabolomics to characterize SARS-CoV-2-associated changes in the gut microbiota from young (2-month-old) and aged (22-month-old) hamsters, a valuable model of COVID-19. We show that age-related dysfunctions in the gut microbiota are linked to disease severity and long-term sequelae in older hamsters. Our data also reveal age-specific changes in the composition and metabolic activity of the gut microbiota during both the acute phase (day 7 post-infection, D7) and the recovery phase (D22) of infection. Aged hamsters exhibited the most notable shifts in gut microbiota composition and plasma metabolic profiles. Through an integrative analysis of metagenomics, metabolomics, and clinical data, we identified significant associations between bacterial taxa, metabolites and disease markers in the aged group. On D7 (high viral load and lung epithelial damage) and D22 (body weight loss and fibrosis), numerous amino acids, amino acid-related molecules, and indole derivatives were found to correlate with disease markers. In particular, a persistent decrease in phenylalanine, tryptophan, glutamic acid, and indoleacetic acid in aged animals positively correlated with poor recovery of body weight and/or lung fibrosis by D22. In younger hamsters, several bacterial taxa (Eubacterium, Oscillospiraceae, Lawsonibacter) and plasma metabolites (carnosine and cis-aconitic acid) were associated with mild disease outcomes. These findings support the need for age-specific microbiome-targeting strategies to more effectively manage acute viral pneumonia and long-term disease outcomes.PMID:40172215 | DOI:10.1080/19490976.2025.2486511
Metabolomics Analysis as a Tool in Periodontitis Diagnosis: A Systematic Review
Clin Exp Dent Res. 2025 Feb;11(1):e70095. doi: 10.1002/cre2.70095.ABSTRACTOBJECTIVES: This study aims to summarize recent studies available on untargeted metabolomics employed for periodontitis diagnosis, from saliva and gingival crevicular fluid samples, to identify recurring metabolites with biomarker-value potential. A secondary objective was to analysudurue the protocols of existing studies, to facilitate further research.MATERIAL AND METHODS: Three databases were electronically searched for relevant studies (PubMed, Web of Science, Scopus). Risk of bias assessment was performed using the Newcastle-Ottawa scale (NOS). Data was extracted from studies, regarding general characteristics and conclusions, population characteristics, periodontal protocols, and metabolomics protocols. Metabolic pathway analysis was performed for recurrent metabolites.RESULTS: After screening 405 studies, 13 studies (10 using saliva samples, 3 using GCF samples) were included. 22 metabolites were identified in more than one study and included into the pathway analysis. Butyrate, lactate, isoleucine, glucose, pyruvate, isovalerate, hypoxanthine/xanthine, proline, valine, phenylalanine, and ethanol were most frequently encountered and were found upregulated in periodontitis patients compared to periodontally healthy patients.CONCLUSIONS: Metabolomics could provide valuable opportunities in validating potential biomarkers or diagnosis panels, contributing to the screening, prognosis, progression and monitoring of periodontitis. Further studies on larger populations and using established protocols are needed. (PROSPERO CRD42023470339).PMID:40172143 | DOI:10.1002/cre2.70095
Unraveling hepatic consequences of intrauterine growth restriction and catch-up growth: insights from histological, biochemical and metabolomic analysis in rats
Int J Dev Biol. 2025 Mar 25. doi: 10.1387/ijdb.240147me. Online ahead of print.ABSTRACTIntrauterine growth restriction (IUGR) is increasingly recognized as a significant risk factor for metabolic disorders in adulthood. Employing a multi-faceted approach encompassing histopathological, immunohistochemical, biochemical, Western-blotting, and metabolomics analyses, this study aimed to elucidate potential metabolite markers of IUGR, and catch-up growth-related metabolic disturbances and the underlying metabolic pathways implicated in IUGR pathogenesis. This study cohort comprised 54 male siblings from 20 Sprague-Dawley female young rats. On the 19th day of gestation, half of the pregnant rats underwent bilateral uterine artery ligation, while the remaining half underwent a simulated surgical intervention involving solely peritoneal incisions. Blood and liver samples were collected from the pups after attaining catch-up growth at the postnatal weeks 2, 4, and 8. IUGR rats exhibited a spectrum of changes including histological abnormalities, altered apoptosis rates, oxidative stress markers, and mitochondrial energy metabolism. Metabolomic analysis revealed dysregulation in multiple metabolic pathways encompassing galactose, propanoate, glycerolipid, cysteine, methionine, and tyrosine metabolism, among others. Notably, disturbances were observed in butanoate, glutathione metabolism, valine, leucine, and isoleucine biosynthesis and degradation, citrate cycle, aminoacyl-tRNA biosynthesis, as well as glycolysis/gluconeogenesis. Our metabolomics analysis provides insights into the potential disease susceptibility of individuals born with IUGR, including obesity, diabetes, heart failure, cancer, mental retardation, kidney and liver diseases, and cataracts. These findings underscore the intricate interplay between intrauterine conditions and long-term metabolic health outcomes, highlighting the need for further investigation into preventive and therapeutic strategies aimed at mitigating the risk of metabolic diseases in individuals with a history of IUGR.PMID:40172029 | DOI:10.1387/ijdb.240147me
Oral Neisseria gonorrhoeae Promotes KSHV Lytic Replication
J Med Virol. 2025 Apr;97(4):e70304. doi: 10.1002/jmv.70304.ABSTRACTThe human oral cavity contains highly diverse microbes, including bacteria, fungi, and viruses. Human herpesviruses are ubiquitous pathogens, and the oral cavity is conducive to the replication, dissemination, and pathogenesis of human herpesviruses. Herpesviruses are generally pathogenic in immunodeficient individuals, such as AIDS patients and organ transplant recipients. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma and two types of rare lymphoma, that is, primary effusion lymphoma and multicentric Castleman's disease. Mounting evidence indicates that KSHV viral load positively correlates with ongoing bacterial infection in the oral cavity, suggesting that bacteria potentially stimulate KSHV replication. However, the mechanism by which oral bacteria may promote KSHV lytic replication is poorly understood. In this study, we performed DNA sequencing and 16S ribosomal RNA analysis of saliva samples of AIDS-KS patients. A correlation analysis identified a panel of oral residential bacteria and uncommon ones that paralleled with KSHV viral load. Performing functional assays, we discovered that the sexually transmitted Neisseria gonorrhoeae (N.g.) significantly increased KSHV lytic replication. Increased KSHV lytic replication was evidenced by elevated levels of mRNA and proteins of viral lytic genes. N.g. stimulation increases the expression of RTA that drives viral lytic replication. Metabolomic analysis reveals the synergistic effect of KSHV and N.g. on cellular metabolism, including the glycolysis and purine and pyrimidine synthesis, that likely underpins the elevated KSHV lytic replication. Findings from our study shed light on the molecular detail of bacteria-virus interaction in the oral cavity and provide references to develop an innovative strategy to treat diseases associated with KSHV.PMID:40171956 | DOI:10.1002/jmv.70304
Metabolomic network reveals novel biomarkers for type 2 diabetes mellitus in the UK Biobank study
Diabetes Obes Metab. 2025 Apr 2. doi: 10.1111/dom.16351. Online ahead of print.ABSTRACTAIMS: To identify hub metabolic biomarkers that constructively shape the type 2 diabetes mellitus (T2DM) risk network.MATERIALS AND METHODS: We analysed data from 98 831 UK Biobank participants, confirming T2DM diagnoses via medical records and International Classification of Diseases codes. Totally 168 circulating metabolites were quantified by nuclear magnetic resonance at baseline. Metabolome-wide association studies with Cox proportional hazards models were performed to identify statistically significant metabolites. Network analysis was applied to compute topological attributes (degree, betweenness, closeness and eigencentrality) and to detect small-world features (high clustering, short path lengths). Identified metabolites were used with XGBoost models to assess risk prediction performance.RESULTS: Over a median 12-year follow-up, 114 metabolites were significantly associated with T2DM risk and clustered into three distinct small-world modules. Total triglycerides and large high-density lipoprotein (HDL) cholesterol emerged as the pivotal biomarkers in the 'risk' and 'protective' modules, respectively, as evidenced by their high eigencentrality. Moreover, total branched-chain amino acids (BCAAs) exhibited small-world network characteristics exclusively in pre-T2DM individuals, suggesting them as a potent early indicators. GlycA demonstrated high closeness centrality in females, implying a female-specific risk biomarker.CONCLUSIONS: By constructing a metabolic network that captures the complex interrelationships among circulating metabolites, our study identified total triglycerides and large HDL cholesterol as central hubs in the T2DM risk metabolome network. BCAA and GlycA emerged as alarm indicators for pre-T2DM individuals and females, respectively. Network analysis not only elucidates the topological functional roles of biomarkers but also addresses the limitations of false positives and collinearity in single-metabolite studies, offering insights for metabolic pathway research and precision interventions.PMID:40171861 | DOI:10.1111/dom.16351
Metabolomic analysis of urethane-induced lung carcinogenesis in rats and the ameliorative effect of Qi-Yu-San-Long decoction
Anal Methods. 2025 Apr 2. doi: 10.1039/d4ay02165g. Online ahead of print.ABSTRACTLung carcinogenesis (LC) is a kind of disease, which threatens human health seriously. Metabolomic research on bio-fluids and tissues is crucial for elucidating the pathogenesis of LC and understanding the therapeutic mechanisms of medicines. In this study, we established a rat model for LC by induction with urethane. The anti-tumor effect of Qi-Yu-San-Long decoction (QYSLD) on LC was assessed through morphology changes, histopathological examination, and inflammation levels. Utilizing the metabolomics technique based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), we investigated the metabolic changes in the plasma and lungs of LC rats and explored the ameliorative effects of QYSLD on the molecular levels. Functional biomarkers associated with QYSLD in LC rats were identified and relatively quantified. The results manifested that, in contrast to the control group, the number of tumor nodules and inflammation levels in the LC model group increased significantly, indicating that the LC rat model was successfully built. After QYSLD treatment, the morphology and lesion degree of LC rats were greatly improved. A total of 23 differential metabolites between the control group and the urethane-induced LC group were screened through plasma and lung tissue metabolomics studies, of which 20 were considerably modulated after QYSLD treatment. Metabolic pathway analysis revealed that the pathogenesis of LC and the therapeutic effects of QYSLD primarily involved glycerophospholipid metabolism, ether lipid metabolism, sphingolipid metabolism, and arachidonic acid metabolism. Our findings provide a potential intracellular metabolite profile for urethane-induced LC and demonstrate that QYSLD exerts anti-tumor effects on LC by modulating multiple metabolic pathways.PMID:40171836 | DOI:10.1039/d4ay02165g
Differential effects of ellagic acid on non-alcoholic fatty liver disease in mice: grouped by urolithin A-producing capacity
Food Funct. 2025 Apr 2. doi: 10.1039/d5fo00440c. Online ahead of print.ABSTRACTEllagic acid (EA) exhibits protective effects on non-alcoholic fatty liver disease (NAFLD). However, the ability to produce urolithins and the health benefits associated with EA consumption differ considerably among individuals. Therefore, the different effects of EA on high-fat and high-fructose diet (HFFD)-induced NAFLD, considering variability in urolithin-producing ability, were explored. Our results showed that EA could effectively reduce body weight, lipid accumulation and insulin resistance, and improve oxidative stress and inflammation in NAFLD mice. The metabolomics analysis indicated that liver metabolism disorder induced by HFFD was obviously improved by EA mainly through the regulation of unsaturated fatty acid biosynthesis and amino acid metabolism. In particular, the improvement effect of EA on NAFLD in mice with high urolithin A production was better than that in their low counterparts. Moreover, EA treatment reshaped the gut microbiota imbalance caused by HFFD. Specifically, compared to the model group, the lower abundances of Faecalibaculum (by 95.11%), Ruminococcus_torques_group (by 208.14%), Clostridium_sensu_stricto_1 (by 449.37%), and Ileibacterium (by 172.64%), while higher abundances of Verrucomicrobia and Akkermansia (by 425.0%) were observed in the high-UroA-producing group (p < 0.05). This study provided new insights into EA's anti-NAFLD effectiveness and suggested that the response capacity of the gut microbiota to EA greatly determined the performance of EA in alleviating the development of NAFLD.PMID:40171675 | DOI:10.1039/d5fo00440c
Salidroside attenuates sepsis-induced acute kidney injury by inhibiting ferroptosis
J Asian Nat Prod Res. 2025 Apr 2:1-15. doi: 10.1080/10286020.2025.2481291. Online ahead of print.ABSTRACTSalidroside is a traditional Chinese medicine with multiple pharmacological activities such as anti-inflammatory and antioxidant properties, while acute kidney injury (AKI) is a common sepsis-induced acute inflammatory response. Using transcriptomics combined with metabolomics, this study identifies arachidonic acid metabolism-associated ferroptosis as an important mechanism for salidroside to improve sepsis-induced AKI (SI-AKI).PMID:40171644 | DOI:10.1080/10286020.2025.2481291
Unveiling the substrate specificity of the ABC transporter Tba and its role in glycopeptide biosynthesis
iScience. 2025 Mar 3;28(4):112135. doi: 10.1016/j.isci.2025.112135. eCollection 2025 Apr 18.ABSTRACTGlycopeptide antibiotics (GPA) such as vancomycin are essential last-resort antibiotics produced by actinomycetes. Their biosynthesis is encoded within biosynthetic gene clusters, also harboring genes for regulation, and transport. Diverse types of GPAs have been characterized that differ in peptide backbone composition and modification patterns. However, little is known about the ATP-binding cassette (ABC) transporters facilitating GPA export. Employing a multifaceted approach, we investigated the substrate specificity of GPA ABC-transporters toward the type-I GPA balhimycin. Phylogenetic analysis suggested and trans-complementation experiments confirmed that balhimycin is exported only by the related type I GPA transporters Tba and Tva (transporter of vancomycin). Molecular dynamics simulations and mutagenesis experiments showed that Tba exhibits specificity toward the peptide backbone rather than the modifications. Unexpectedly, deletion or functional inactivation of Tba halted balhimycin biosynthesis. Combined with proximity biotinylation experiments, this suggested that the interaction of the active transporter with the biosynthetic machinery is required for biosynthesis.PMID:40171492 | PMC:PMC11960670 | DOI:10.1016/j.isci.2025.112135
Phosphatidylcholine Ameliorates Palmitic Acid-Induced Lipotoxicity by Facilitating Endoplasmic Reticulum and Mitochondria Contacts in Intervertebral Disc Degeneration
JOR Spine. 2025 Mar 31;8(2):e70062. doi: 10.1002/jsp2.70062. eCollection 2025 Jun.ABSTRACTBACKGROUND: Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal disorder with substantial socioeconomic impacts. Despite its high prevalence, the pathogenesis of IDD remains unclear, and effective pharmacological interventions are lacking. This study aimed to investigate metabolic alterations in IDD and explore potential therapeutic targets by analyzing lipotoxicity-related mechanisms in nucleus pulposus (NP) cells.METHODS: Metabolomics and magnetic resonance spectroscopy were utilized to profile metabolic changes in NP tissues from advanced-stage IDD. Transcriptomics and metabolomics integration were performed to identify key regulatory pathways. In vitro experiments using human NP cells exposed to palmitic acid were conducted to evaluate endoplasmic reticulum (ER) stress, mitochondrial dysfunction, lipid droplet accumulation, and senescence. Phosphatidylcholine supplementation was tested for its ability to mitigate lipotoxicity, with ER-mitochondria interactions and mitochondrial oxidation capacity assessed as mechanistic endpoints.RESULTS: Our findings revealed an abnormal lipotoxic condition in NP cells from advanced-stage IDD. Furthermore, we identified abnormal accumulation of triglycerides and palmitic acid in NP cells from IDD. The palmitic acid accumulation resulted in endoplasmic reticulum stress, mitochondrial damage, lipid droplet accumulation, and senescence of NP cells. By integrating transcriptomics and metabolomics analyses, we discovered that phosphatidylcholine plays a role in regulating palmitic acid-induced lipotoxicity. Notably, phosphatidylcholine level was found to be low in the endoplasmic reticulum and mitochondria of advanced-stage NP cells. Phosphatidylcholine treatment alleviated palmitic acid-induced lipid droplet accumulation and senescence of NP cells by modulating ER-mitochondria contacts and mitochondrial oxidation capacity.CONCLUSION: Phosphatidylcholine emerges as a potential therapeutic agent to counteract lipotoxic stress by modulating organelle interactions and mitochondrial function. These findings advance our understanding of IDD pathogenesis and provide a novel metabolic target for therapeutic development.PMID:40171442 | PMC:PMC11956213 | DOI:10.1002/jsp2.70062
Metabolomic effects of intrauterine meloxicam perfusion on histotroph in dairy heifers during diestrus
Front Vet Sci. 2025 Mar 18;12:1528530. doi: 10.3389/fvets.2025.1528530. eCollection 2025.ABSTRACTIn ruminants, conceptus elongation is a crucial developmental process that depends on uterine lumen fluid (ULF) and coincides with a period of high pregnancy loss. Prostaglandins (PGs) play indispensable roles in conceptus elongation and implantation. However, the effects of uterus-derived PGs on the uterine environment remain unclear. To explore the metabolic pathways and metabolites induced by endometrium-derived PGs that may affect conceptus elongation and implantation in dairy cows, we investigated the biochemical composition of ULF following intrauterine perfusion of meloxicam from days 12 to 14 of the estrous cycle. Intrauterine administration of meloxicam significantly downregulated the prostaglandin-related metabolites in the ULF. A total of 385 distinct metabolites, primarily clustered within lipids and lipid-like molecules, organic acids and derivatives, organoheterocyclic compounds, and benzenoids, were identified. The metabolite network analysis identified 10 core metabolites as follows: S-adenosylhomocysteine, guanosine, inosine, thymidine, cholic acid, xanthine, niacinamide, prostaglandin I2, 5-hydroxyindoleacetic acid, and indoleacetaldehyde. The pathway enrichment analysis revealed three significantly altered metabolic pathways: arachidonic acid metabolism, tryptophan (Trp) metabolism, and linoleic acid metabolism. A total of five metabolites-guanosine, inosine, thymidine, butyryl-l-carnitine, and l-carnitine-were associated with attachment and pregnancy loss and could serve as predictors of fertility. This global metabolic study of ULF enhances our understanding of histotroph alternations induced by uterus-derived PGs during diestrus in dairy cows, with implications for improving dairy cow fertility.PMID:40171410 | PMC:PMC11959509 | DOI:10.3389/fvets.2025.1528530
Cotton under heat stress: a comprehensive review of molecular breeding, genomics, and multi-omics strategies
Front Genet. 2025 Mar 18;16:1553406. doi: 10.3389/fgene.2025.1553406. eCollection 2025.ABSTRACTCotton is a vital fiber crop for the global textile industry, but rising temperatures due to climate change threaten its growth, fiber quality and yields. Heat stress disrupts key physiological and biochemical processes, affecting carbohydrate metabolism, hormone signaling, calcium and gene regulation and expression. This review article explores cotton's defense mechanism against heat stress, including epigenetic regulations and transgenic approaches, with a focus on genome editing tools. Given the limitations of traditional breeding, advanced omics technologies such as GWAS, transcriptomics, proteomics, ionomics, metabolomics, phenomics and CRISPR-Cas9 offer promising solutions for developing heat-resistant cotton varieties. This review highlights the need for innovative strategies to ensure sustainable cotton production under climate change.PMID:40171219 | PMC:PMC11959566 | DOI:10.3389/fgene.2025.1553406
Disrupted gut microbiota promotes the progression of chronic kidney disease in 5/6 nephrectomy mice by <em>Bacillus pumilus</em> gavage
Front Cell Infect Microbiol. 2025 Mar 18;15:1548767. doi: 10.3389/fcimb.2025.1548767. eCollection 2025.ABSTRACTBACKGROUND: Our previous study identified differences in the gut microbiota between patients with chronic kidney disease (CKD) and healthy individuals. We observed that antibiotic-treated mice exhibited symptoms similar to those of patients with CKD after receiving a gut microbiota transplant from patients with CKD. Bacillus pumilus (B. pumilus), an alien microorganism to both human and mouse gut microbiota, possesses antibiotic properties that can alter the microbial community structure. Therefore, this study aimed to explore how changes in the gut microbiota structure induced by the oral gavage of B. pumilus affect the progression of CKD. We sought to identify the gut microbes and metabolic pathways associated with CKD to lay the groundwork for future clinical probiotic applications in patients with CKD.METHODS: We constructed sham-operated and 5/6 nephrectomy mice as the sham control (SC) and CKD models, respectively. CKD models were divided into a control group (CG) and an intervention group (IG). After 16 weeks of normal feeding, the IG were treated with B. pumilus by oral gavage, while SC and CG were treated with PBS once daily, 5 days per week, for 7 weeks. Fecal samples were collected for 16s rRNA sequencing and metabolomic analysis, kidneys were harvested for histological examination, and the colon was used for RT-PCR analysis.RESULTS: B. pumilus intervention exacerbated gut microbial homeostasis in CKD mice and increased serum creatinine and urea nitrogen levels, further aggravating kidney damage. 16s rRNA and metabolomic analysis revealed that Parvibacter and Enterorhabdus were probiotics related to kidney function, while Odoribacter was associated with kidney injury. Metabolomic analysis showed that glycerophospholipid and lysine metabolism were upregulated in CKD model mice, correlating with kidney damage.CONCLUSION: This study shows that changes in the gut microbiota can affect the kidneys through gut metabolism, confirming that the lack of probiotics and the proliferation of harmful bacteria leading to gut microbiota dysbiosis are drivers of CKD progression. Our findings provide a basis for clinical interventions using gut microbes and offer a reference for targeted probiotic therapy.PMID:40171160 | PMC:PMC11959065 | DOI:10.3389/fcimb.2025.1548767
Diets shape thermal responses in Chinese giant salamanders by altering liver metabolism
Front Microbiol. 2025 Mar 18;16:1546912. doi: 10.3389/fmicb.2025.1546912. eCollection 2025.ABSTRACTDiet can influence the thermal performance of ectotherms, providing potential strategies for biological conservation in the context of global warming. The endangered Andrias davidianus is susceptible to heat stress due to energy deficiency in the liver when fed a worm-based diet rich in carbohydrates. A fish-based diet, rich in protein and lipids, improves their thermal performance, but the underlying physiological mechanisms remain unclear. In this study, we used metabolomics and metagenomics to examine the combined effects of temperature (15, 20, and 25°C) and diet (fish-based and worm-based) on liver metabolism and gut microbiota. Our results show that both temperature and diet shape liver metabolism, with several vital metabolic pathways (e.g., TCA cycle and sulfate metabolism) regulated by their combined effects. Notably, diet-dependent thermal responses in energy metabolism were observed, with fish-fed salamanders exhibiting a marked upregulation of the TCA cycle intermediates under heat stress, a response absent in worm-fed individuals. Given the role of TCA cycle in heat susceptibility of A. davidianus, these findings suggest that the TCA cycle likely mediates the interactive effects of temperature and diet on thermal performance. We then examined whether the gut microbiota is also a target of interactive effects or a mediator of the diet's influence on liver metabolism. While both temperature and diet shape microbiota composition, functional shifts occur only in response to temperature, indicating that the microbiota is not a major link between diet and liver metabolism. However, several bacterial groups (e.g., Thiosulfatimonas and Alcanivorax), jointly regulated by temperature and diet, correlate with liver metabolites, suggesting alternative, function-independent pathways through which dietary-related microbial changes may influence liver metabolism and even thermal tolerance. Overall, this study provides molecular insights into the dietary modulation of thermal performance in A. davidianus and highlight the potential of dietary microbial management strategies for amphibian conservation.PMID:40170926 | PMC:PMC11959279 | DOI:10.3389/fmicb.2025.1546912
<em>Trigonella foenum-graecum</em> L. protects against renal function decline in a mouse model of type 2 diabetic nephropathy by modulating the PI3K-Akt-ERK signaling pathway
Front Pharmacol. 2025 Mar 18;16:1566723. doi: 10.3389/fphar.2025.1566723. eCollection 2025.ABSTRACTOBJECTIVES: Trigonella foenum-graecum L. (HLB) exhibits promising pharmacological properties for the treatment of type 2 diabetic nephropathy (DN). This study aims to enhance the understanding of HLB's pharmacodynamic effects and elucidate the mechanisms underlying its therapeutic potential in DN.METHODS: The pharmacodynamic effects of HLB were initially evaluated in a murine DN model through the oral administration of an aqueous extract of HLB. The primary bioactive constituents were subsequently identified using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Network pharmacology analysis was integrated with these data to uncover potential molecular targets of HLB in DN. Key renal metabolites were profiled using untargeted metabolomics, followed by metabolic pathway enrichment analysis conducted with the MetaboAnalyst 6.0 platform, which facilitated the identification of relevant metabolic pathways through which HLB modulates DN. Finally, quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot (WB) techniques were employed to validate the expression levels of key genes and proteins, thereby confirming the molecular mechanisms underlying the effects of HLB in DN.RESULTS: Animal experiments indicated that HLB significantly improved blood glucose regulation and renal function while reducing oxidative stress and abnormalities in lipid metabolism in diabetic mice. A total of 34 compounds and 159 potential therapeutic targets were identified as key active components of HLB. The untargeted metabolomics analysis revealed 61 critical metabolites, among which the PI3K-Akt-ERK signaling pathway-known to be involved in diabetes-was highlighted as a crucial pathway. QRT-PCR and WB analyses demonstrated that HLB upregulated the expression of MAPK1, MAPK3, AKT1, and PI3K.CONCLUSION: These results suggest that HLB may alleviate DN by modulating oxidative stress and lipid metabolism. Its effects are likely mediated through the PI3K-Akt-ERK signaling pathway, along with the upregulation of MAPK1, MAPK3, AKT1, and PI3K expression. This study lays the groundwork for further investigations into the molecular mechanisms underlying HLB's action in DN.PMID:40170727 | PMC:PMC11959092 | DOI:10.3389/fphar.2025.1566723