PubMed

J Anal Methods Chem. 2026 Feb 27;2026:4116313. doi: 10.1155/jamc/4116313. eCollection 2026.ABSTRACTInborn errors of metabolism such as phenylketonuria (PKU) and maple syrup urine disease (MSUD) can cause severe developmental problems. Both conditions can lead to harmful levels of keto acids in biofluids-phenylpyruvic acid (PPA) in PKU and branched-chain α-keto acids in MSUD. Monitoring urinary keto acids helps track dietary adherence and reduces the risk of metabolic crisis. However, current at-home tests are qualitative and difficult to interpret, while existing metabolomic assays require expensive equipment and must be conducted in a lab. This study aimed to develop a simple, quantitative, rapid, at-home assay for detecting multiple urinary keto acids associated with PKU and MSUD. A modified two-step 2,4-dinitrophenylhydrazine (DNPH)-based multimetabolite assay was developed, where sodium hydroxide (NaOH) converts the yellow hydrazone precipitate to a stable amber solution, enabling quantification of multiple keto acids (700-7200 μM) within 10 min. The assay was validated using spiked urine samples and adapted into a prototype at-home kit using caprolactam-immobilized NaOH. Nuclear magnetic resonance (NMR)-based metabolomics was used as a reference method to authenticate readings from a PKU patient. Correlation studies demonstrated strong linearity for MSUD (R 2 = 0.91-0.96)- and PKU (R 2 = 0.95-0.99)-spiked samples. Quantification of keto acids in authentic PKU urine samples showed excellent agreement with the results of quantitative NMR-based metabolomics assays (R 2 = 0.99). Low-cost, at-home colorimetric tests for urinary keto acids could enable screening, detection, and monitoring of PKU and MSUD in the 90% of the world without access to advanced metabolic clinics.PMID:41767879 | PMC:PMC12949077 | DOI:10.1155/jamc/4116313

Kidney Med. 2026 Jan 5;8(3):101245. doi: 10.1016/j.xkme.2026.101245. eCollection 2026 Mar.ABSTRACTRATIONALE & OBJECTIVE: Additional investigations into the causal effects of kidney function on various metabolites, particularly lipoprotein lipids in detailed subfractions of lipoprotein particles, in the general population are warranted.STUDY DESIGN: Integrated cross-sectional observational and Mendelian randomization (MR) analyses.SETTING & PARTICIPANTS: We included 157,541 participants aged 40-69 years from the UK Biobank study, a population-scale prospective cohort. Genetic instruments for estimated glomerular filtration rate (eGFR) were developed from the Chronic Kidney Disease Genetics genome-wide association study meta-analysis results, which comprised 567,460 individuals of European ancestry.EXPOSURE: eGFR for observational analysis and genetically predicted eGFR for MR analysis.OUTCOMES: Each of the 178 metabolites from recently updated metabolomics data, including detailed lipoprotein components within 14 subclasses of lipoprotein particles.ANALYTICAL APPROACH: Observational analysis was performed using multivariate linear regression adjusted for various clinicodemographic characteristics. A 2-sample MR analysis was performed using the random-effects inverse-variance weighted method as the main MR method.RESULTS: In the integrated results of the observational and MR analyses, 25 metabolites were causally associated with eGFR. A lower eGFR causally decreased lipoprotein components of high-density lipoprotein and several of its subclasses, particularly medium-sized high-density lipoprotein. Conversely, a lower eGFR causally increased triglyceride levels in smaller-sized very low-density lipoprotein and intermediate-density lipoprotein, as well as increased lipoprotein particle concentrations and total lipids in small very low-density lipoprotein. Additionally, a lower eGFR causally increased the ratio of monounsaturated fatty acids to total fatty acids and that of apolipoprotein B to apolipoprotein A-1.LIMITATIONS: Possibility of false-negative findings when integrating observational and MR analyses.CONCLUSIONS: Decreased kidney function causally aggravates lipoprotein lipid profiles; therefore, clinicians should closely monitor the lipid profiles of individuals with impaired kidney function.PMID:41767688 | PMC:PMC12937174 | DOI:10.1016/j.xkme.2026.101245

Food Chem X. 2026 Feb 18;34:103688. doi: 10.1016/j.fochx.2026.103688. eCollection 2026 Feb.ABSTRACTThis study integrated metabolomics, electronic tongue, and molecular docking to investigate how a multi-stage steam-drying process influences the flavor characteristics of pomelo black tea. Results showed that continuous steam-drying can significantly reduce bitterness and umami, and it could also promote the hydrolysis of flavonoid glycosides such as naringenin and the accumulation of organic acids such as linolenic acid, thereby increasing acidity while reducing bitterness. Volatile component analysis indicated that heat-sensitive terpenes such as γ-terpinene was significantly reduced due to oxidative degradation. Aldehydes and esters, including undecanal and neryl acetate, might compensate for this loss of aroma through thermal conversion. This research also found that hydrogen bonds and hydrophobic interactions were key to the binding of aroma compounds to olfactory receptors. Overall, this study provides molecular- and sensory-level evidence linking moist heat processing to coordinated changes in taste- and aroma-related compounds in pomelo black tea.PMID:41767662 | PMC:PMC12938864 | DOI:10.1016/j.fochx.2026.103688

Research (Wash D C). 2026 Feb 19;9:1081. doi: 10.34133/research.1081. eCollection 2026.ABSTRACTExposures that disrupt the immune system can affect human health. This study aimed to understand immune variability influenced by exposures from the perspectives of systems biology and multiomics. We recruited 1,001 healthy participants and collected 183 exposures, 1,332 immunophenotypes, whole blood transcriptome, and plasma metabolome. Through exposure-immune wide association analysis, we identified 81 significant signals, with sleep and diet emerging as dominant exposures affecting the immunity. Sleep and diet influence the proportions of innate immune cells and the expression levels of immune cell surface proteins such as CD85j and CD16, respectively. Notably, distinct from the increase in interleukin-1β secretion caused by short-term late sleep onset, long-term late sleep onset triggered chronic inflammation with more metabolic changes. On the basis of the intracorrelation structure of exposure data, composite exposures were constructed and were found to have additional effects on immunophenotypes. Bidirectional mediation analysis revealed that sleep effects on immunity are commonly linked to the transcriptome, whereas dietary influences on immunity are primarily associated with the metabolome. We quantified the mediation effects of exposures, omics, and immunophenotypes and further demonstrated that these effects reflect human immune health or chronic diseases. Our study drew a comprehensive map of "exposure-immunome-omics" and is expected to provide guidance for future health assessment and management.PMID:41767601 | PMC:PMC12943795 | DOI:10.34133/research.1081

Front Oncol. 2026 Feb 12;15:1703182. doi: 10.3389/fonc.2025.1703182. eCollection 2025.ABSTRACTINTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) originates from intrahepatic bile duct epithelial cells and its global incidence is rising. Surgery remains the primary treatment, but postoperative recurrence rates remain high.METHODS: We analyzed ICC patients' gut microbiota at four stages (preoperative, 7 days postoperative, 1 month postoperative, and during recurrence) using 16S rRNA sequencing and their serum metabolome via LC-MS/MS. Correlations among gut microbiota, metabolome, and clinical indicators were investigated, and candidate microorganisms and metabolites were integrated for multiomics clustering and staging.RESULTS: This revealed significant increases in Bacteroides, Veillonella, and Enterococcus in ICC patients compared to healthy controls across all stages, suggesting these bacteria as potential markers of ICC progression. Microbial and metabolite changes were observed, with gut microbes influencing ICC development through kynurenic acid, linoleic acid, creatine, cholic acid, L-arginine, and the tumor microenvironment. Multiomics analysis showed that cholangiocarcinoma staging improves patient prognosis, particularly highlighting bile acids' role in type II hepatic phenotypes related to cholesterol metabolism.DISCUSSION: Our study provides insights into ICC microbiome and metabolome associations with clinical features and survival.PMID:41767584 | PMC:PMC12935644 | DOI:10.3389/fonc.2025.1703182

Front Microbiol. 2026 Feb 13;17:1726349. doi: 10.3389/fmicb.2026.1726349. eCollection 2026.ABSTRACTPseudomonas protegens CHA0 and other fluorescent pseudomonads suppress plant diseases by producing a number of metabolites with antibiotic activities in the rhizosphere. However, limited information is available on the physiological functions of most of these metabolites. We herein describe the detection of 3-mercaptopropionic acid (3-MPA), a thiol compound, based on the metabolome of the supernatant of strain CHA0. 3-MPA exhibited antibiotic activity against oomycete and fungal pathogens and suppressed Pythium damping-off and root rot in cucumber. 3-MPA also exhibited antibiotic activity without direct contact with pathogens, indicating the volatilization effect of this compound. We identified a homologous gene encoding 3-MPA dioxygenase in the CHA0 genome and the production level of 3-MPA was elevated in a 3mdo-negative mutant. Growth inhibitory activity against oomycete and fungal pathogens and plant protection efficacy exhibited by the 3mdo-negative mutant were stronger than those of wild-type CHA0. These results suggest that 3-MPA is biocontrol factor of strain CHA0.PMID:41767571 | PMC:PMC12947264 | DOI:10.3389/fmicb.2026.1726349

Front Microbiol. 2026 Feb 12;17:1765127. doi: 10.3389/fmicb.2026.1765127. eCollection 2026.ABSTRACTINTRODUCTION: Severe acute pancreatitis (SAP) is frequently complicated by intestinal barrier disruption, bacterial translocation, and systemic inflammation. Emerging evidence indicates that gut microbial metabolic disturbances, particularly altered short-chain fatty acids (SCFAs), may contribute to epithelial injury, yet the mechanistic links between microbial metabolites and host inflammatory signaling remain insufficiently defined. We therefore investigated whether Lactobacillus paracasei LP18 protects against SAP-associated intestinal barrier dysfunction by reshaping gut metabolism, restoring butyrate availability, and attenuating NF-κB activation.METHODS: A mouse model of SAP was established and animals received LP18 intervention. Intestinal injury and barrier integrity were evaluated by histopathology, tight junction protein assessment, and inflammatory cytokine measurements. Metabolic alterations were profiled using untargeted metabolomics and targeted quantification of SCFAs was performed. NF-κB signaling was assessed by measuring p65 phosphorylation and nuclear translocation. Correlation analyses were conducted to relate SCFA levels to barrier markers.RESULTS: SAP induced pronounced epithelial injury, including villus atrophy, Tight junction disruption, elevated pro-inflammatory cytokines, and robust NF-κB activation. Untargeted metabolomics revealed extensive metabolic perturbations, with significant changes in butanoate metabolism and lipid-associated pathways. LP18 administration partially reversed these abnormalities and shifted the metabolomic profile toward a mucosa-protective signature. Targeted SCFA analysis showed marked butyrate depletion in SAP mice, whereas LP18 significantly increased butyrate levels and partially normalized acetate and propionate. Higher butyrate concentrations correlated with improved intestinal integrity and reduced inflammatory response. Mechanistically, LP18 suppressed inflammatory signaling by inhibiting p65 phosphorylation and nuclear translocation, consistent with attenuated NF-κB pathway activation.CONCLUSION: Lactobacillus paracasei LP18 attenuates SAP-associated intestinal inflammation and barrier dysfunction, primarily through modulation of gut microbial composition, restoration of butyrate-associated metabolic profiles, and suppression of NF-κB-related inflammatory signaling.PMID:41767557 | PMC:PMC12936515 | DOI:10.3389/fmicb.2026.1765127

J Diabetes Metab Disord. 2026 Feb 26;25(1):90. doi: 10.1007/s40200-026-01918-3. eCollection 2026 Jun.ABSTRACTPURPOSE: Poor diet quality is a known risk factor for type 2 diabetes and related outcomes, including declines in insulin sensitivity. Biological changes that occur in response to diet may explain this relationship.METHODS: This study was conducted in a cohort of young adults (the MetaAIR study, n = 77, 52% female, 57% Hispanic). High dimensional mediation analyses (HIMA) were performed to identity potential metabolite, protein, and miRNA mediators of the relationship between the Healthy Eating Index-2015 (HEI) and insulin sensitivity (Matsuda Index) over a four year follow up period. Features identified by HIMA and significant after correction for multiple comparisons (q < 0.05) were assessed using causal mediation analyses. The indirect effects and proportion mediated by each feature were calculated independently.RESULTS: Each point increase in HEI was associated with a 0.051 (95% CI:0.004, 0.098) point increase in Matsuda Index. Four potential mediators were identified using HIMA: three metabolites (5Z,8Z,11Z-eicosatrienoic acid, pipecolic acid, and biotin), and one protein (F9). Each of these features exhibited a positive indirect effect and independently mediated between 35 and 43% of the total effect. No miRNAs were selected as potential mediators.CONCLUSION: These findings suggest that specific metabolites and proteins may mediate the association between diet and diabetes-related outcomes such as declines in insulin sensitivity, likely through pathways related to inflammation. F9, biotin, pipecolic acid, and 5Z,8Z,11Z-eicosatrienoic acid may be potential targets for monitoring efforts for diet adherence or disease prevention.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-01918-3.PMID:41767436 | PMC:PMC12946319 | DOI:10.1007/s40200-026-01918-3

Front Endocrinol (Lausanne). 2026 Feb 12;17:1736270. doi: 10.3389/fendo.2026.1736270. eCollection 2026.ABSTRACTINTRODUCTION: High-altitude environments impose unique physiological stresses that may alter metabolic dysregulation in individuals with type 2 diabetes mellitus (T2DM). However, the key determinants driving altitude-specific metabolic differences in diabetic patients remain insufficiently characterized. This study aimed to identify critical metabolic biomarkers and pathways distinguishing T2DM patients residing at high versus low altitudes.METHODS: Serum samples were collected from 100 participants stratified into four matched groups: high-altitude T2DM (H_T2DM), high-altitude healthy controls (H_HC), low-altitude T2DM (L_T2DM), and low-altitude healthy controls (L_HC). Metabolomic profiling was performed using ultra-performance liquid chromatography‒quadrupole time-of-flight mass spectrometry (UPLC‒Q‒TOF‒MS) to compare endogenous metabolite abundance across groups. Pathway topology analysis was conducted to annotate functional metabolic pathways, and multicenter validation was implemented to verify the robustness of candidate biomarkers.RESULTS: A total of 26 differentially abundant endogenous metabolites were identified in H_T2DM patients relative to the other three groups, with 18 metabolites significantly upregulated and 8 downregulated. Pipecolic acid, lauric acid, guanosine, and kaempferol were identified as potential early biomarkers for high-altitude diabetes, collectively achieving a prediction accuracy of 92%. These biomarkers were linked to core metabolic pathways including lysine degradation, fatty acid biosynthesis, and purine metabolism. Multicenter validation further confirmed guanosine as the most robust and altitude-specific biomarker for T2DM.DISCUSSION: Our comprehensive metabolomic analysis reveals distinct metabolic perturbations in T2DM patients under high-altitude conditions, highlighting guanosine as a unique biomarker for identifying altitude-related diabetic metabolic dysregulation. These findings advance our understanding of the pathophysiological mechanisms underlying T2DM in high-altitude environments and provide a potential diagnostic target for clinical management of diabetic populations in such regions.PMID:41767400 | PMC:PMC12935616 | DOI:10.3389/fendo.2026.1736270

Front Endocrinol (Lausanne). 2026 Feb 13;17:1754743. doi: 10.3389/fendo.2026.1754743. eCollection 2026.ABSTRACTOBJECTIVE: Diabetic foot ulcers (DFU) are a severe complication with high amputation and mortality rates, involving profound metabolic dysregulation. Current treatments lack interventions targeting the metabolic microenvironment. Chenodeoxycholic acid (CDCA) regulates glucose/lipid metabolism and inflammation, but its role in DFU remains unknown. This study aims to identify key metabolites in the serum of patients with diabetic foot ulcers. For the first time, it focuses on and identifies CDCA, a key bile acid, as an endogenous protective factor, and validates the biological role of CDCA in promoting wound healing, thereby providing a foundation for novel therapeutic strategies targeting the "metabolic microenvironment."METHODS: Untargeted metabolomics (UHPL-MS/MS) was performed on serum from 18 healthy controls, 18 diabetes mellitus (DM) patients, and 18 DFU patients. Multivariate statistics and logistic regression were used to identify differential metabolites and protective factors. In vitro, human skin fibroblasts under high glucose (30 mM) were treated with CDCA (5-25 nM). Proliferation, migration, and repair gene expression were assessed.RESULTS: Clinical evaluation revealed that DF patients exhibited more pronounced systemic inflammation (elevated hs-CRP, ESR, and WBC), coagulation abnormalities (increased fibrinogen and D-dimer levels), and higher prevalence of vascular complications compared to other groups. Metabolomic analysis identified 41 significantly altered metabolites between the DM and DF groups, among which CDCA was markedly downregulated in the DF group (fold change = 0.66, VIP = 2.09, P = 0.008). Logistic regression analysis confirmed CDCA as an independent protective factor against DFU (OR = 0.429, 95% CI: 0.225-0.815, P = 0.010). In vitro studies demonstrated that CDCA dose-dependently reversed high glucose-induced impairment of HSF function, significantly enhancing cell proliferation and migration, and upregulating mRNA expression of PCNA, α-SMA, and Vimentin.CONCLUSION: This study identifies CDCA as a key protective metabolite in DF. Reduced serum CDCA levels are independently associated with increased risk of DF. Functional evidence confirms that CDCA mitigates high glucose-induced fibroblast dysfunction and promotes wound repair processes. Targeting the CDCA signaling pathway or supplementing CDCA may represent a novel therapeutic strategy for DF by remodeling the "metabolic microenvironment".PMID:41767398 | PMC:PMC12945834 | DOI:10.3389/fendo.2026.1754743

iScience. 2026 Feb 5;29(3):114916. doi: 10.1016/j.isci.2026.114916. eCollection 2026 Mar 20.ABSTRACTUbiquitin-specific protease 5 (USP5) is frequently overexpressed in lung adenocarcinoma (LUAD) and correlates with advanced stage and poor prognosis. This study demonstrates that USP5 binds directly to CD73 and removes K48-linked polyubiquitin chains, thereby blocking its proteasomal degradation and increasing CD73 protein stability. In contrast, the E3 ligase tripartite motif-containing protein 28 (TRIM28) promotes CD73 ubiquitination and turnover. Functionally, USP5 enhances LUAD cell proliferation, migration, invasion, and tumor growth in vivo in a CD73-dependent manner. Metabolomic profiling and Seahorse assays reveal that the USP5/CD73 axis activates PI3K/AKT/mTOR signaling and drives glycolytic reprogramming, augmenting lactate production. Moreover, this axis contributes to acquired resistance to osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI); combined inhibition of USP5 and osimertinib synergistically induces apoptosis and suppresses tumor growth in vitro and in vivo. These findings establish USP5-mediated stabilization of CD73 as a central mechanism underlying glycolytic metabolism and osimertinib resistance in LUAD, highlighting the USP5/CD73 pathway as a promising prognostic indicator and therapeutic target for LUAD treatment.PMID:41767275 | PMC:PMC12936848 | DOI:10.1016/j.isci.2026.114916

Front Psychiatry. 2026 Feb 13;17:1736206. doi: 10.3389/fpsyt.2026.1736206. eCollection 2026.ABSTRACTMental disorders remain diagnosed primarily through symptom-based classification systems that overlook biological heterogeneity, preventing the identification of mechanistically distinct patient subgroups and precluding pathophysiology-guided treatment selection. Metabolomics offers a promising pathway towards precision psychiatry by capturing dynamic biochemical readouts at the functional endpoint of the omics cascade, integrating genetic, environmental, and pharmacological influences on cellular metabolism. Over the past 15 years, untargeted and targeted metabolomics studies using nuclear magnetic resonance spectroscopy and mass spectrometry have identified consistent patterns of metabolic dysregulation across psychiatric disorders, particularly involving amino acid metabolism, lipid signaling, energy homeostasis, and oxidative stress pathways. Schizophrenia presents disruptions in arginine and proline metabolism, glutathione metabolism, and energy-related processes. Bipolar disorder shows perturbations in branched-chain and aromatic amino acids, kynurenine pathway, and tricarboxylic acid cycle dysfunction with phase-specific metabolic signatures. Major depressive disorder exhibits widespread alterations in amino acid turnover, bioenergetic processes, membrane lipid homeostasis, and glutamate-GABA cycling, with treatment-responsive metabolic changes. Despite these advances, substantial challenges remain: heterogeneous findings with disorder overlap, limited replication cohorts, predominance of cross-sectional designs, confounding by medication and lifestyle factors, pre-analytical variability, and high-dimensional data complexity. Future research requires harmonized multi-site protocols, longitudinal validation studies, multi-platform analytical approaches, integration with genomics, proteomics, and digital phenotyping, and implementation of artificial intelligence frameworks to enhance phenotype discrimination and predictive accuracy. In this mini-review, we provide an overview of current methodologies, major findings, strengths, challenges, and emerging directions in psychiatric metabolomics, with the goal of facilitating the translation of metabolomic insights into clinically applicable, personalized psychiatric treatment.PMID:41767152 | PMC:PMC12946017 | DOI:10.3389/fpsyt.2026.1736206

Front Immunol. 2026 Feb 6;17:1682589. doi: 10.3389/fimmu.2026.1682589. eCollection 2026.ABSTRACTBACKGROUND: Oral lichen planus (OLP) is a chronic T-cell-mediated inflammatory disorder of unknown etiology. Accumulating evidence has demonstrated elevated cholesterol levels in OLP, and its oxidation products --oxysterols have been implicated in T cell dysfunction. However, whether the oxysterol is involved in OLP pathogenesis remains to be fully elucidated.METHODS: Metabolomics was performed to profile oxysterols in the plasma of OLP patients, followed by functional enrichment analysis. Single-cell RNA sequencing was utilized to characterize gene expression dysregulation in tissue-resident T cells isolated from OLP lesions. Flow cytometry, immunofluorescence, and qRT-PCR were collectively used to quantify Ca2+ concentration, cell apoptosis, protein expression, intracellular signaling, and gene transcription levels. Functional validation was conducted through a co-culture model and Transwell migration assays to assess the cytotoxic and migratory capacity of OLP T cells.RESULTS: The oxysterol profiles were aberrant in OLP plasma, with marked accumulation of 7-ketocholesterol (7KC). Functional analysis identified significant enrichment of differential metabolites in androstenedione metabolism. 7KC upregulated the expression of cholesterol regulators (SREBP2/LXR) in OLP T cells. Pro-7-ketocholesterogenic gene sets were dysregulated in OLP tissues, with localized T cells exhibiting enriched Ca2+ -NFATc1 signaling and coordinated F-actin polymerization/ITGAL (LFA-1α) upregulation, positively correlating with migration signatures. Peripheral OLP T cells showed elevated Ca2+, nuclear NFATc1, F-actin polymerization, and LFA-1α, all of which, along with ITGAL/IL1B/CCL4/IL6 levels, were further potentiated by 7KC treatment. 7KC was confirmed to enhance migrations of primary OLP T cells and OLP plasma-pretreated Jurkat T cells toward LPS-treated keratinocytes, without affecting keratinocyte apoptosis. Furthermore, CM4620-mediated blockade of Ca2+ -NFATc1 pathway in OLP T cells inhibited 7KC-induced NFATc1 activation, reduced the expressions of F-actin and its modulators ACTB/DIAPH1, and IL1B/CCL4/IL6 gene expressions, with migration suppressions of both primary OLP T cells and OLP plasma-pretreated Jurkat T cells.CONCLUSIONS: 7KC could promote T cell migration through Ca2+ -NFATc1 pathway-mediated F-actin polymerization and expression of IL1B/CCL4/IL6 in OLP.PMID:41766904 | PMC:PMC12946749 | DOI:10.3389/fimmu.2026.1682589

Aquac Nutr. 2026 Feb 27;2026:9336162. doi: 10.1155/anu/9336162. eCollection 2026.ABSTRACTViral diseases represent one of the major threats to the global aquaculture industry. In recent years, the relationship between gut microbiota and viral infections in fish has garnered increasing attention. The gut microbiota contributes critically to fish health and is involved in antiviral defense through immune regulation, secretion of microbial metabolites, as well as enhancement of barrier function. The gut microbiota, host immunity, and viral infection form a complex and dynamic interaction network. A substantial body of 16S rRNA and metabolomics correlation studies has indicated that viral infections can alter the gut microbiota in fish, while changes in the gut microbiota can, in turn, influence viral infection. In this review, we summarize the regulatory effects of gut microbiota on fish viral infections, explore the interactions between the gut microbiota, immune system, and viral pathogenesis, and discuss future research directions and potential application prospects. By outlining the three-dimensional interaction network of "microbiota-immune-virus" in fish, this review not only lays a theoretical foundation for developing targeted microecological strategies for green disease control but also provides an evolutionary perspective for understanding host-microbe coevolution in vertebrates.PMID:41766780 | PMC:PMC12948727 | DOI:10.1155/anu/9336162

Plant Physiol. 2026 Mar 2:kiag106. doi: 10.1093/plphys/kiag106. Online ahead of print.ABSTRACTL-lysine (Lys) has been explored as a potential cyanobactericide due to its inhibitory effects on cyanobacterial growth at micromolar concentrations, comparable to many antibiotics. Here, we investigated the early metabolic and physiological responses of the model cyanobacterium Synechocystis sp. PCC 6803 to Lys exposure. Physiological analyses revealed cell enlargement, oxidative stress, and photosynthesis inhibition, leading to growth arrest. Metabolomic profiling indicated disruptions in peptidoglycan biosynthesis, evidenced by the accumulation of L-/D-alanine, meso-diaminopimelate, and D-Ala-D-Ala, suggesting interference with cell wall integrity. Furthermore, levels of energy metabolites and other amino acids, including tyrosine, tryptophan, valine, and iso-/leucine, were significantly altered, implying broader metabolic impacts of Lys toxicity. To explore potential resistance mechanisms, we used a CRISPRi-based genetic screen to identify key genes involved in relieving Lys toxicity. The Bgt permease system, responsible for basic amino acid uptake, was essential for acquiring Lys resistance, as a bgtA mutant exhibited normal growth on elevated Lys concentrations, thereby validating our CRISPRi screen. Additionally, UirR, a DNA-binding response regulator, and genes linked to c-di-AMP signaling, seemed implicated in Lys metabolism. Deletion of the c-di-AMP synthase gene increased Lys sensitivity, supporting a role for c-di-AMP in cell wall homeostasis and osmotic stress regulation. Altogether, our findings explored the early metabolic responses and physiological consequences of Lys exposure in Synechocystis, demonstrating its effects on peptidoglycan biosynthesis, amino acid metabolism, and nucleotide biosynthesis. This, as well as the identification of key genetic factors contributing to Lys resistance, provides insights into cyanobacterial physiology and the potential application of Lys in bloom-control strategies.PMID:41766623 | DOI:10.1093/plphys/kiag106

Biomed Chromatogr. 2026 Apr;40(4):e70406. doi: 10.1002/bmc.70406.ABSTRACTSiegesbeckiae herba (SH) with a cold nature exerts therapeutic effects including dispelling wind-dampness, benefiting joints. This study aims to explore the effects of SH and its fractionated components on neuroendocrine metabolism functions in heat syndrome rats and to clarify the property attribution of each component. The main components of SH were isolated via modern separation techniques. A heat syndrome rat model was established by administration of levothyroxine sodium. Metabolomics was employed to screen differential expressed metabolites (DEMs) and metabolic pathways, and indicators related to neuroendocrine metabolism were determined. A total of 107 DEMs involving 17 pathways were screened out. It was found that SH and its fractions could inhibit the abnormally activated metabolic pathways in hot syndrome rats. Among them, the terpenoids fraction showed the optimal regulatory effect on neurotransmitter imbalance, excessive activation of the hypothalamic-pituitary-thyroid axis, and energy/substance metabolism disorders and was confirmed as the main material basis for the cold nature of SH. This study demonstrates that SH and its fractionated components exert therapeutic effects on heat syndromes by regulating the neuroendocrine energy metabolism and related pathways. This provides scientific support for the clinical syndrome differentiation application and further development of SH.PMID:41766560 | DOI:10.1002/bmc.70406

J Anim Sci Biotechnol. 2026 Mar 2;17(1):35. doi: 10.1186/s40104-026-01352-8.ABSTRACTBACKGROUND: Transitioning to a high-grain (HG) diet significantly alters rumen fermentation by increasing the production of short-chain fatty acids (SCFAs) and lowering rumen pH, which may contribute to subacute ruminal acidosis (SARA) and damage to the ruminal epithelium. Rapid adaptation of rumen epithelium to these metabolic shifts is essential to maintain homeostasis, but the transcriptional mechanisms underlying this adaptation remain poorly understood.RESULTS: We analyzed the temporal progression of gene expression and metabolomic profile in rumen papillae collected during low-grain feeding (LG) and one week after transitioning to a HG diet (HG1), or four weeks after (HG4) in cows classified as susceptible or resistant to SARA. RNA sequencing identified 955 differentially expressed genes (DEGs) across time points, revealing a biphasic adaptation pattern. Early responses (HG1) showed moderate transcriptional changes, while HG4 was characterized by substantial transcriptional remodeling. Pathway analysis indicated three major functional categories affected during adaptation: cellular stress response, metabolic adaptation, and protein processing. Notably, sterol biosynthesis genes showed transient upregulation at HG1 followed by downregulation at HG4, coinciding with morphological changes in rumen wall thickness and n-butyrate concentration in rumen fluid. Correlation analyses comparing gene expression patterns and metabolite level changes triggered by the dietary transition revealed potential links between metabolic and transcriptional adaptation. Of particular interest, valerate levels at HG1 correlated with genes involved in tissue remodeling at HG4, implying that valerate may contribute to delayed epithelial responses. Next, transcriptional differences between SARA-susceptible and SARA-resistant animals included genes related to inflammation, cell structure, and metabolism that persisted across all time points, suggesting underlying intrinsic differences in SARA susceptibility that are present before and persist during dietary challenge. Key genes consistently differentially under-expressed in SARA-susceptible animals, CCDC196 and MYO7B, represent potential biomarkers for SARA predisposition. Finally, the SARA-resistant group showed a greater number of transcriptome-metabolome correlations, suggesting more coordinated epithelial responses to diet change compared to the SARA-susceptible group.CONCLUSIONS: Our findings provide insights into the molecular mechanisms underlying rumen adaptation to HG diets and individual variation in SARA susceptibility, providing a basis for developing strategies to optimize dietary transitions in ruminant production systems.PMID:41765993 | DOI:10.1186/s40104-026-01352-8

J Environ Sci (China). 2026 Apr;162:153-163. doi: 10.1016/j.jes.2025.11.022. Epub 2025 Nov 11.ABSTRACTMicrobial remediation of hexavalent chromium (Cr(VI)) contaminants is believed to be effective, and Hermetia illucens can realize the bioremediation of contaminants through biotransformation. However, the synergistic effects of larval gut microbiota and its associated microbial metabolites mediate the resistance and reduction of Cr(VI) remain largely unrecognized. To obtain further details, the feasibility of Cr(VI) reduction through larval biotransformation was investigated, and the interaction between the role of gut bacteria and the function of their metabolites was clarified. The larvae demonstrated tolerance to the Cr(VI) stress, and finally achieved Cr(VI) reduction to Cr(III) by biotransformation, resulting in a relative content of Cr(VI) to the total chromium element in the residual substrate reduced to 1.11%. Myroides, Ulvibacter, Paenalcaligenes, Dysgonomonas, Campylobacter, and RsaHf231 in larval gut responded strongly to Cr(VI) stress. Meanwhile, the highest level of Cr(VI) stress caused differences in gut microbial metabolism with 124 metabolites being screened as upregulated and 150 metabolites as downregulated compared to that without Cr(VI) stress. Especially, Dysgonomonas, Enterococcus, Myroides, Paenalcaligenes and Ulvibacter were mainly associated with some metabolites that can be used as electron donors or electronic mediators to assist microbial growth and reduce or detoxify Cr(VI). These findings indicate that larval biotransformation is a green application for remediating Cr(VI), and gut microbiota and its associated metabolites can be further mined for Cr(VI) reduction and detoxification.PMID:41765514 | DOI:10.1016/j.jes.2025.11.022

Food Chem Toxicol. 2026 Feb 27:116037. doi: 10.1016/j.fct.2026.116037. Online ahead of print.ABSTRACTTo investigate the toxicological effects after individual or combined sub-chronical exposure to oxidized triacylglycerols, aldehydes, and 3-MCPDE formed during thermal processing of high-fat foods, this study implemented transcriptome-metabolome analysis of renal tissues in Kunming mice, supplemented with urine metabolomics study. Transcriptomic analysis highlighted perturbations in the PI3K-Akt signaling pathway, while metabolomic and integrated analyses both identified disruptions in glycerophospholipid metabolism. Urine metabolomic results further corroborated renal dysfunction, with altered tryptophan and purine metabolism. Results revealed that the exposure of three toxicants induced multi-organ metabolic network encompassing the kidney, liver, and even nervous system. Toxic effects were less pronounced when the three toxicants were exposed in combination while compared to their individual effects, suggesting the necessity for further investigation in the potential antagonistic mechanisms. Results provide critical insights into the co-exposure toxicity and interaction mechanisms of thermally induced toxicants in high-fat foods, offering toxicological foundations for establishing safety regulations.PMID:41765338 | DOI:10.1016/j.fct.2026.116037

Environ Res. 2026 Feb 27:124140. doi: 10.1016/j.envres.2026.124140. Online ahead of print.ABSTRACTOrganophosphorus flame retardants (OPFRs) are associated with intestinal injury. Bisphenol A bis(diphenyl phosphate) (BDP), an emerging OPFR that is widely present in organisms and humans, may induce intestinal toxicity, yet the effect and underlying mechanism remains unclear. In this study, zebrafish were exposed to BDP at 2, 20 and 200 μg/L for 21 days. Distinct histopathological changes in the intestine of zebrafish were observed, and the relative expressions of mucus secretion and tight junction related genes (MUC-2, Occuludin a and ZO-1) were all downregulated. Through the integrated analysis combining metabolomics and metagenomics, the results demonstrated that BDP exposure downregulated the abundances of microbiota Peptostreptococcus, Clostridium, Bombilactobacillus and Sporolactobacillus in zebrafish intestines, to depress tryptophan metabolism and eventually reduce the abundances of tryptophan metabolites. As a result, the expression of AhR, an important receptor activated by tryptophan metabolites, was inhibited to downregulate IL-22 expression, promoting intestinal toxicity. In vivo experiment with indole-3-propionic acid supplement alleviated the pathological changes, which further confirmed that BDP destroyed microbiota-tryptophan metabolism homeostasis to interfere with the AhR-IL-22 axis, eventually promoted pathological toxicity in the intestines. This study highlights vulnerability of intestines to BDP, and provides first insight into the mechanism through which BDP threats intestinal health.PMID:41765316 | DOI:10.1016/j.envres.2026.124140