PubMed

Analyst. 2026 Jan 21. doi: 10.1039/d5an00943j. Online ahead of print.ABSTRACTSynovial fluid is a clinically valuable biofluid for studying joint diseases through metabolomic analysis. However, given the viscoelastic nature of this biofluid its analysis is challenging. Indeed, the lack of standardised pre-analytical processing protocols for synovial fluid metabolomics potentially introduces significant variability that can compromise data reliability and hinder the application/interpretation of results. This study systematically assesses how common sample handling variables including sample dilution, freeze-thaw cycling, blood staining and viscosity reduction (via hyaluronidase digestion and bead beating) affect the metabolomic profile of synovial fluid. Using a combination of untargeted GC-ToF-MS and UHPLC-MS (in both electrospray ionisation modes; ESI+ and ESI-) for the profiling of both polar and non-polar metabolites, we evaluated changes in detectable metabolite numbers, small molecule class distribution and relative abundances in a collection of synovial fluid samples. Sample dilution had the most pronounced impact on metabolite read-outs, significantly reducing detectable metabolite numbers. Blood staining introduced distinct metabolites and resulted in the artificial increase in the relative abundance of three metabolites including adenine, hypoxanthine and 4-fluoro-DL-tryptophan. Bead beating enhanced the detection of a broad range of lipid species particularly in the UHPLC ESI+ analysis. Freeze-thaw cycling and hyaluronidase treatment had minimal effects on overall metabolite quantities or composition. These findings underscore the importance of optimising and standardising synovial fluid sample handling to ensure reproducibility and to enable accurate interpretation of metabolomic data for the study of disease mechanisms and biomarker discovery.PMID:41563355 | DOI:10.1039/d5an00943j

Microbiol Spectr. 2026 Jan 21:e0284325. doi: 10.1128/spectrum.02843-25. Online ahead of print.ABSTRACTResearch has demonstrated that resveratrol (RES) and β-hydroxy-β-methylbutyric acid (HMB) promote gastrointestinal health by altering the intestinal microbiome. The present study aimed to evaluate the impacts of RES and HMB on the bacterial community composition and metabolomic profiles of the jejunum in Tibetan sheep. A total of 120 male Tibetan lambs, with an average initial body weight of 16.87 ± 0.31 kg, were randomly assigned to four experimental groups according to a 2×2 factorial design. The experimental diets contained 11.19% protein diet, or 12.69% protein diet supplemented with RES/HMB (H-RES-HMB and L-RES-HMB, respectively), and 11.19% protein diet, or 12.69% protein diet without supplemented with RES/HMB (LCP and HCP, respectively). The findings indicated a significant increase in jejunal digestive enzyme activities (α-amylase and chymotrypsin), antioxidant capacity (catalase, glutathione peroxidase, and superoxide dismutase), and immune responses (including immunoglobulins A, G, and M) in the H-RES-HMB group, in contrast to a notable decrease in markers of oxidative stress and pro-inflammatory cytokines (interleukin 1β, interleukin 6, and tumor necrosis factor alpha) (P < 0.05). Morphological assessments revealed a significant reduction in crypt depth within the H-RES-HMB group (P < 0.05). Among the short-chain fatty acids, butyric acid concentration was significantly elevated in the H-RES-HMB group (P < 0.05). Additionally, mRNA expression levels of barrier-associated genes, including OCLN, Muc-2, and ZO-1 in the jejunum, were significantly enhanced in the H-RES-HMB group. Microbial community analysis demonstrated that the inclusion of RES and HMB in the 14% protein diet resulted in an increase in the relative abundance of Firmicutes, Bacillus, and Methanobrevibacter, while simultaneously reducing the abundance of Proteobacteria, Escherichia, and Shigella. Notably, the increased abundance of these beneficial bacteria was positively correlated with butyric acid concentrations. Furthermore, metabolomic analysis indicated higher levels of L-Arginine and His-Lys in the H-RES-HMB group, which also showed a positive correlation with butyric acid concentration, whereas isovaleric acid, D-xylose, and diacetyl concentrations were lower in this group. In conclusion, the findings suggest that a 14% protein diet is more effective in enhancing jejunal morphology and barrier function. Supplementation with RES and HMB in this diet resulted in elevated concentrations of volatile fatty acids, particularly butyric acid, by modulating microbial community composition (notably Firmicutes, Bacillus, and Methanobrevibacter) and metabolite profiles (including Gamma-aminobutyric acid, Succinate, L-Arginine, and His-Lys). A synergistic effect was found between the crude protein level (14%) and dietary RES/HMB on villus phenotype, digestive enzyme capacity, and antioxidant activity.IMPORTANCETo thrive in harsh, high-altitude environments, Tibetan sheep require efficient nutrient absorption. Our study shows that a diet with optimal protein (12.69%) supplemented with natural additives-resveratrol and β-hydroxy-β-methylbutyric acid-significantly enhances gut health. This dietary regimen strengthened the intestinal barrier, suppressed harmful inflammation, and boosted local immunity. Furthermore, it enriched the gut microbiome with beneficial butyric acid-producing bacteria, a key nutrient for intestinal cells. This research establishes a practical nutritional strategy to improve intestinal function and overall resilience in Tibetan sheep, supporting sustainable livestock production in challenging plateau regions.PMID:41563063 | DOI:10.1128/spectrum.02843-25

Methods Protoc. 2026 Jan 8;9(1):8. doi: 10.3390/mps9010008.ABSTRACTCerebrospinal fluid (CSF) is a key biological matrix that reflects the physiological and pathological states of the central nervous system (CNS). It supports brain function by regulating ionic balance, facilitating molecular transport, and clearing metabolic waste. In this article, we present a standardized protocol for CSF collection along with an integrative multiplatform metabolomic workflow that combines proton nuclear magnetic resonance spectroscopy (1H-NMRS) and high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Integrating these complementary analytical modalities enhances metabolite coverage and improves analytical robustness, enabling a more comprehensive and reliable characterization of the CSF metabolome. This workflow supports the discovery of potential biomarkers and advances our understanding of neurochemical alterations within the CNS.PMID:41562986 | DOI:10.3390/mps9010008

Med Sci (Basel). 2026 Jan 11;14(1):38. doi: 10.3390/medsci14010038.ABSTRACTThe major subtypes of leukemia show sex differences. This review summarizes current knowledge and identifies gaps regarding sex differences across acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and chronic lymphoblastic leukemia in epidemiology, mortality and survival rates, risk factors, and epigenetic, metabolomic, and sex-specific patterns. Males have higher incidence and mortality rates of leukemia compared to females, emphasizing the importance of biological sex. Underreporting of sex differences in leukemia is highlighted, suggesting that sex is often overlooked as a research variable. A significant clinical observation is that women demonstrate higher overall survival rates but experience more severe treatment-related toxicity. Clinically, women tend to survive longer but experience more severe side effects. In contrast, a significant clinical observation in pediatric leukemia contradicts this enigma, suggesting that sex differences may be less pronounced during childhood. These differences play a significant role in how the disease develops. This review presents a sex-based perspective for hematological and biochemical patterns, genetic risk factors, environmental, lifestyle, and parental risk factors, epigenetics and metabolites. Furthermore, males and females might have different responses to the same toxic, environmental, and hormonal exposures. Trying to understand these disparities better based on molecular mechanisms is considered an approach for precision medicine.PMID:41562928 | DOI:10.3390/medsci14010038

J Dev Biol. 2026 Jan 3;14(1):3. doi: 10.3390/jdb14010003.ABSTRACTMaternal nutrition during gestation profoundly influences fetal growth, organogenesis, and long-term offspring performance through developmental programming. Among the molecular mechanisms responsive to maternal nutrient availability, one-carbon metabolism plays a central role by integrating folate, methionine, choline, and vitamin B12 pathways that regulate methylation, nucleotide synthesis, and antioxidant defense. These processes link maternal nutritional status to epigenetic remodeling, cellular proliferation, and redox balance during fetal development. Mitochondria act as nutrient sensors that translate maternal metabolic cues into bioenergetic and oxidative signals, shaping tissue differentiation and metabolic flexibility. Variations in maternal diet have been associated with shifts in fetal amino acid, lipid, and energy metabolism, suggesting adaptive responses to constrained intrauterine environments. This review focuses on the molecular interplay between one-carbon metabolism, mitochondrial function, and metabolomic adaptation in developmental programming of ruminant livestock. Understanding these mechanisms offers opportunities to design precision nutritional strategies that enhance fetal growth, offspring productivity, and long-term resilience in livestock production systems.PMID:41562863 | DOI:10.3390/jdb14010003

Proteomes. 2026 Jan 4;14(1):1. doi: 10.3390/proteomes14010001.ABSTRACTBACKGROUND: The arsenic-responsive repressor, ArsR, has long been understood as a canonical regulator of the arsRBC operon, which confers resistance to arsenic stress. However, recent studies suggest a broader regulatory scope for ArsR. Here, we investigated the proteomic landscape of Escherichia coli strains with and without ArsR to elucidate ArsR as an activator in both non-stressing and arsenic-stressing conditions.METHODS: Using mass-spectrometry-based shotgun proteomics and statistical analyses, we characterized the differential abundance of proteins across AW3110 (ΔarsRBC), AW3110 complemented with arsR, and wild-type K-12 strains under control and arsenite-stressed conditions.RESULTS: Our study shows that ArsR influences proteomic networks beyond the ars operon, integrating metabolic and redox responses crucial for cellular adaptation and survival. This suggests that ArsR has a significant role in gut microbiome metabolomic profiles in response to arsenite. Proteins involved in alanine, lactaldehyde, arginine, thioredoxin, and proline pathways were significantly elevated in strains where ArsR was detected, both with and without arsenite. We identified proteins exhibiting an "ArsR-dependent" activation pattern, highlighting ArsR's potential role in redox balance and energy metabolism.CONCLUSIONS: These findings challenge the classical view of ArsR as a repressor and position it as a pleiotropic regulator, including broad activation.PMID:41562852 | DOI:10.3390/proteomes14010001

J Xenobiot. 2026 Jan 15;16(1):14. doi: 10.3390/jox16010014.ABSTRACTFoundries represent complex exposure scenarios where metals, particulate matter, and combustion by-products coexist, posing potential cumulative biological effects. Urinary metabolic profiles from 64 foundry workers and 78 residents living in surrounding areas were investigated using multivariate statistical modeling. Differences in urinary metabolite patterns were observed between the two groups, including lower levels of several amino acids (e.g., valine, alanine, tyrosine, and tryptophan) and tricarboxylic acid intermediates (e.g., citrate and succinate), together with higher levels of selected branched-chain amino acid catabolites (e.g., 3-hydroxyisobutyrate and erythro-2,3-dihydroxybutyrate) in workers. Variations in gut microbiota-related metabolites, such as phenylacetylglycine and p-cresol sulphate, were also detected. Based on these metabolic patterns, potential molecular mechanisms related to energy metabolism, oxidative stress and host-microbiome interaction are discussed as interpretative hypotheses. The comparison between workers and residents was interpreted, taking into account differences in demographic and lifestyle characteristics between groups. Overall, the results indicate that occupational exposure in foundries is associated with measurable differences in urinary metabolic profiles, demonstrating that the applied NMR-based metabolomic strategy is capable of capturing early biological effects and supporting its potential as a non-invasive and holistic biomonitoring tool for evaluating the health impact of complex occupational exposures.PMID:41562773 | DOI:10.3390/jox16010014

Infect Dis Rep. 2026 Jan 12;18(1):10. doi: 10.3390/idr18010010.ABSTRACTBACKGROUND/OBJECTIVES: Metabolomics has emerged as a powerful systems-biology tool for deciphering dynamic metabolic alterations occurring during infectious diseases and following vaccination. While genomics and proteomics provide extensive molecular and regulatory information, metabolomics uniquely reflects the biochemical phenotype associated with infection, immune activation, and immunometabolic reprogramming. The objective of this review is to provide an integrated analysis of metabolomics applications across both neglected tropical diseases (NTDs) and non-NTD pathogens, highlighting its dual role in biomarker discovery and vaccine response evaluation.METHODS: A comprehensive literature-based synthesis was conducted to examine metabolomic studies in infectious diseases and vaccinology. Metabolic perturbations associated with specific pathogens, as well as vaccine-induced metabolic changes and correlates of immune responses, were systematically analyzed and compared across NTD and non-NTD contexts.RESULTS: Distinct pathogen- and vaccine-associated metabolic signatures were identified, reflecting alterations in glycolysis, amino acid metabolism, lipid remodeling, and immunoregulatory pathways. Comparative analysis revealed both shared and disease-specific metabolic biomarkers across NTDs and non-NTD infections. Importantly, vaccine-related metabolic correlates were shown to mirror immune activation states and, in some cases, predict immunogenicity and response durability.CONCLUSIONS: This review bridges metabolomics research in infectious disease pathogenesis and vaccine immunology across the NTD and non-NTD spectrum. By integrating these domains, it introduces the concept of "metabolic immuno-signatures" as predictive and translational tools for evaluating vaccine efficacy and immune response outcomes.PMID:41562665 | DOI:10.3390/idr18010010

Clin Exp Rheumatol. 2026 Jan 21. doi: 10.55563/clinexprheumatol/ksopba. Online ahead of print.ABSTRACTOBJECTIVES: To investigate gut microbial alteration and their functional consequences in obesity (OB)-related knee osteoarthritis (OA) by integrating microbiome with metabolomic, proteomic, and dietary data.METHODS: Fecal and fasting plasma samples were collected from 91 knee OA patients and 12 OA-free controls, classified into four subgroups based on OB and OA status: 66 OB+OA+, 25 OB-OA+, 5 OB+OA-, and 7 OB-OA-. 16S rRNA gene sequencing was performed to profile gut microbiota. MaAsLin2 modelling was applied, and dietary intake was incorporated into the models. Plasma metabolomics (n=630 metabolites) and proteomics (n=5,416 proteins) were integrated with microbial signatures to assess functional associations.RESULTS: OB+OA+ patients exhibited significantly lower a- and β-diversity than OB-OA+ (p<0.05). Seventeen microbial taxa were identified to be significantly associated with OB+OA+ (all p<7.65×10-5 after correcting tests for 654 ASVs), and 16 of them remained significant after adjustment for age, sex, antibiotic use, and dietary intake. PICRUSt2-based predictive analysis on these taxa suggested that bile acid biosynthesis was upregulated in OB+OA+ group. These taxa were correlated with 376 metabolites (p<0.05) with enrichment in fatty acid biosynthesis, linoleic/arachidonic acid metabolism, and propanoate metabolism pathways. They were also associated with 146 proteins (p<0.001) with enrichment in PI3K-Akt signalling, ECM-receptor interaction, and lipid/atherosclerosis pathways.CONCLUSIONS: OB+OA+ patients exhibited significant gut microbial dysbiosis associated with systemic metabolic and proteomic alterations relevant to OA pathophysiology. The microbiome-metabolome-proteome axis may provide mechanistic insights into worsened OA outcomes in OB individuals and could inform microbiome-targeted interventions.PMID:41562358 | DOI:10.55563/clinexprheumatol/ksopba

Microbiol Immunol. 2026 Jan 21. doi: 10.1111/1348-0421.70039. Online ahead of print.ABSTRACTInfluenza pneumonia is characterized by excessive inflammatory responses that contribute to severe lung injury and mortality. Supersulfides, endogenously produced cysteine-derived persulfides and polysulfides, exert potent antioxidant, anti-ferroptotic, and anti-inflammatory activities; however, their therapeutic potential after disease onset remains unclear. Here, we investigated the efficacy of N-acetylcysteine tetrasulfide (NAC-S2), a highly water-soluble and cell-permeable supersulfide donor, in a mouse model of influenza A virus (IAV)-induced pneumonia. Subcutaneous administration of NAC-S2 rapidly elevated systemic levels of cysteine- and glutathione-derived supersulfides. In therapeutic treatment starting 2 days post-infection, when body weight loss and clinical signs had already developed, NAC-S2 significantly improved survival and mitigated body weight loss compared with vehicle and oxidized NAC controls. Metabolomic analysis revealed that influenza virus infection depleted lung glutathione persulfide (GSSH), while NAC-S2 effectively restored tissue GSSH levels. NAC-S2 treatment markedly reduced pulmonary interleukin (IL)-1β and IL-6 production without affecting viral load or Type-I interferon responses. Furthermore, NAC-S2 suppressed NLRP3 inflammasome activation and gasdermin D expression, leading to decreased infiltration of CD3+ T cells and myeloperoxidase-positive neutrophils. Histopathological analyses confirmed that NAC-S2 ameliorated epithelial injury, interstitial edema, and hemorrhage in infected lungs. Collectively, our findings demonstrate that NAC-S2 exerts therapeutic benefit even after the onset of severe influenza pneumonia, primarily by replenishing supersulfides and alleviating excessive inflammatory responses. Supersulfide donors represent a promising class of adjunctive therapeutics for severe viral pneumonia.PMID:41562319 | DOI:10.1111/1348-0421.70039

Food Funct. 2026 Jan 21. doi: 10.1039/d5fo04897d. Online ahead of print.ABSTRACTHelicobacter pylori (H. pylori) infection is a serious public health concern worldwide. This study evaluated the preventive effects of fucoidan extracted from sea cucumber cooking liquid (Fuc-SC) against gastritis induced by Helicobacter pylori SS1 (Hp SS1) infection. High-dose (150 mg kg-1) Fuc-SC significantly reduced levels of Hp SS1 immunoglobulin G (Hp-IgG) and cytotoxin-related gene A immunoglobulin G (CagA-IgG), while inhibiting urease activity, leading to an approximately 18% reduction in Hp SS1 colonization in the gastric mucosa. Fuc-SC also modulated oxidative stress more effectively than Fuc-LJ, suppressing nitric oxide (NO), malondialdehyde (MDA), and reactive oxygen species (ROS), likely due to its smaller molecular weight and higher sulfate content. Regarding inflammatory regulation, Fuc-SC dose-dependently down-regulated interleukin (IL)-1β, IL-6, T helper 17 (Th17) cells, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α), while up-regulating IL-10. These effects further modulated the expression of the inflammatory protein S100A8 and E-cadherin in the gastric mucosa, alleviating gastric inflammation. Moreover, 16S rRNA and metabolomics analyses revealed that Fuc-SC mitigates inflammatory responses by inhibiting pathogenic bacteria such as Dubosiella and Monoglobus, while promoting probiotics like Lactobacillus and Akkermansia, thereby enhancing the biosynthesis of short-chain fatty acids and beneficial metabolites, including naringenin, afzelechin, and pinocembrin. In summary, Fuc-SC exerts multifaceted protective effects on the gastric mucosa, highlighting its potential as a preventive strategy for H. pylori-associated gastritis.PMID:41562139 | DOI:10.1039/d5fo04897d

Front Mol Biosci. 2026 Jan 5;12:1720876. doi: 10.3389/fmolb.2025.1720876. eCollection 2025.ABSTRACTINTRODUCTION: Keloids are fibroproliferative skin scars characterized by excessive extracellular matrix deposition and a high rate of recurrence. Despite extensive research, their pathogenesis remains incompletely understood and effective curative therapies are lacking.METHODS: RNA sequencing (RNA-seq) and metabolomics were performed to compare gene expression and metabolite profiles between human keloid tissues and normal skin. Single-cell RNA sequencing, immunohistochemistry, and immunofluorescence were used to determine the cellular localization of key genes. In vitro, human fibroblasts were stimulated with glutamate, followed by RNA-seq, quantitative RT-PCR, and ELISA to evaluate inflammatory gene expression and cytokine secretion.RESULTS: Transcriptomic analysis revealed significant enrichment of the neuroactive ligand-receptor interaction pathway in keloid tissue, with marked upregulation of the glutamate receptor subunit GRIN2D. Single-cell and histological analyses demonstrated that GRIN2D is predominantly expressed in fibroblasts. Metabolomic profiling showed significantly increased levels of glutamate and glutamine in keloid tissues. Glutamate stimulation of fibroblasts significantly enhanced the expression and secretion of inflammatory cytokines IL-6 and IL-11, as well as chemokines CXCL2, CXCL3, and CXCL8 (IL-8).DISCUSSION: These results underscore the crucial role of glutamate metabolism in promoting the infammatory functions of fbroblasts. They suggest that glutamate contributes to keloid progression and provides a theoretical basis for targeting glutamte signaling pathway in keloid treatment.PMID:41562114 | PMC:PMC12812582 | DOI:10.3389/fmolb.2025.1720876

Front Immunol. 2026 Jan 5;16:1742855. doi: 10.3389/fimmu.2025.1742855. eCollection 2025.ABSTRACTMetabolic reprogramming has emerged as a central determinant of immune modulation in the post-metastatic tumor immune microenvironment (TIME). Alterations in glycolysis and lactate accumulation, lipid metabolic rewiring, metal-dependent cell death pathways such as ferroptosis and cuproptosis, and the tryptophan-IDO1-kynurenine axis collectively contribute to an immunosuppressive niche that drives tumor progression and therapeutic resistance. These metabolic shifts are not isolated events but are intricately connected with immune-regulatory networks, profoundly influencing the efficacy of immunotherapy. Advances in multi-omics technologies-including metabolomics, proteomics, single-cell sequencing, and spatial omics-have provided unprecedented resolution to decode these complex interactions, enabling the identification of predictive biomarkers, delineation of metabolic-immune signatures, and discovery of therapeutic vulnerabilities. Integrating these multi-layered datasets has paved the way for precision medicine strategies that tailor immunotherapy to patient-specific metabolic and immune contexts. Therapeutically, combining metabolic inhibitors with immune checkpoint blockade, exploiting ferroptosis or cuproptosis to enhance tumor immunogenicity, or modulating amino acid metabolism to reverse immune tolerance are promising strategies to overcome resistance and expand patient benefit. Looking forward, the integration of multi-omics-guided biomarkers, AI-driven analytics, and advanced delivery systems such as nanoparticles and engineered exosomes will accelerate the translation of these insights into clinical practice. Decoding the metabolism-immunity crosstalk through multi-omics not only advances our understanding of metastatic cancer biology but also paves the way for next-generation personalized and adaptive therapies that promise to enhance immunotherapy efficacy, prolong survival, and improve the quality of life for patients with advanced cancers.PMID:41562065 | PMC:PMC12813170 | DOI:10.3389/fimmu.2025.1742855

Environ Health (Wash). 2025 Sep 5;4(1):74-87. doi: 10.1021/envhealth.5c00215. eCollection 2026 Jan 16.ABSTRACTCyclotriphosphazenes (CTPs), widely used as flame-retardant electrolyte additives in lithium batteries, have raised significant environmental and health concerns due to their potential release and human exposure. However, the toxicological effects of CTPs, particularly on pulmonary health, remain poorly understood. This study investigates the impact of long-term CTPs exposure at environmentally relevant doses on lung cells and animal models. In vitro experiments revealed that CTPs exposure impaired mitochondrial function in BEAS-2B cells in a time-dependent manner. Proteomic analysis demonstrated significant alterations in oxidative phosphorylation-related proteins, disrupting the electron transport chain (ETC). Untargeted metabolomics further revealed disruptions in the tricarboxylic acid (TCA) cycle, glutathione metabolism, and purine metabolism, with notably decreased levels of key metabolites. Multiomics integration suggested potential associations between high-dose CTPs exposure and diseases including lipoyltransferase 1 deficiency, Alzheimer's disease, and schizophrenia. In vivo studies confirmed pathological lung damage in mice, including alveolar destruction and pulmonary fibrosis. Additionally, downregulation of N-lauroylsphingosine (NLDP) was identified as a potential metabolic biomarker for CTPs-induced lung injury, offering novel insights for mitigating CTPs' adverse effects. These findings highlight the pulmonary toxicity of CTPs and provide a foundation for future risk assessment and preventive strategies.PMID:41562040 | PMC:PMC12813705 | DOI:10.1021/envhealth.5c00215

Environ Health (Wash). 2025 Sep 9;4(1):88-96. doi: 10.1021/envhealth.5c00128. eCollection 2026 Jan 16.ABSTRACTEpidemiological evidence of the blood metabolic mechanisms through which summer temperatures affect human health is scarce, despite the well-established risks and increasing severity under a warming climate. Based on the Chinese Undergraduates Cohort (CUC), we aim to explore the association between summer temperature exposure and blood metabolomics in young adults. Plasma samples were tested with an untargeted metabolomic analysis. Meteorological data was collected from China Meteorological Data Sharing Service System. The three consecutive months with the highest monthly average temperatures of the whole year were defined as summer. One-way analysis of variance (ANOVA) and the multiple linear regression model were used to assess the effects of summer mean temperature exposure on blood metabolomics, followed by stratified analysis by sex. A total of 1,930 participants, with a mean age of 18.18 ± 0.65 years, were included in this study. The summer mean temperature was 26.03 ± 1.70 °C. Metabolomic analysis identified 54 altered metabolites related to summer mean temperature, of which 7 altered metabolites were enriched in 4 significant metabolic pathways (p < 0.05), which were mainly involved in amino acid and peptide compound metabolism. Stratified analysis results showed that in addition to amino acid metabolism, summer mean temperature exposure also disrupted vitamin metabolism in females. Summer mean temperature could possibly be associated with altered metabolic pathways such as amino acid metabolism, causing inflammation and oxidative stress damage. Females could be more susceptible to summer temperature in terms of disrupted vitamin metabolism.PMID:41562036 | PMC:PMC12813697 | DOI:10.1021/envhealth.5c00128

Front Cell Dev Biol. 2026 Jan 5;13:1747211. doi: 10.3389/fcell.2025.1747211. eCollection 2025.ABSTRACTSelecting embryos with the highest developmental potential remains a decisive step for achieving successful in vitro fertilization outcomes. Conventional evaluation methods such as morphological grading, time-lapse imaging, and preimplantation genetic testing for aneuploidy provide valuable information but are limited by subjectivity, invasiveness, and cost. These challenges have driven increasing interest in non-invasive biomarkers capable of improving the precision and safety of embryo assessment. Emerging evidence indicates that human embryos actively release microRNAs into their surrounding environment, particularly into the spent culture medium and blastocoel fluid. These extracellular microRNAs regulate pathways involved in cell cycle progression, apoptosis, differentiation, and embryo-endometrium communication. Distinct expression signatures, including miR-21-5p, miR-661, and members of the miR-17∼92 cluster, correlate with chromosomal integrity and implantation competence, suggesting their potential as complementary or alternative biomarkers to trophectoderm biopsy. Comparative analyses across digital PCR, quantitative RT-PCR, microarray, and next-generation sequencing platforms reveal both methodological advances and unresolved challenges, such as low RNA yield, contamination risk, and inconsistent normalization strategies. Embryo-derived microRNAs thus represent a promising avenue for non-invasive embryo evaluation, with future clinical translation hinging on robust multicenter validation and integration with imaging, metabolomics, and artificial intelligence-based analytics.PMID:41561630 | PMC:PMC12812889 | DOI:10.3389/fcell.2025.1747211

Brain Behav Immun Health. 2025 Dec 19;51:101164. doi: 10.1016/j.bbih.2025.101164. eCollection 2026 Feb.ABSTRACTBACKGROUND: Climate factors exert a profound influence on human emotional well-being and physical health. Exposure to a humid heat environment is known to precipitate anxiety-like behaviors and exacerbate the clinical manifestations of influenza; concurrently, mounting evidence has demonstrated a bidirectional regulation between the gut microbiota and human health, suggesting a potential link between environmental stress and microbial homeostasis.METHODS: In this study, C57BL/6J male mice were subjected to a humid heat environment for 3 weeks prior to infection with the influenza A virus. Microbiota composition, metabolites, and intestinal mucosal immunity were comprehensively measured. Furthermore, behavioral phenotypes and neurotransmitter levels were assessed to explore their potential correlations with gut dysbiosis.RESULTS: Exposure to a humid heat environment aggravated pulmonary and intestinal tissue damage while reshaping the gut microbiota composition and metabolome. This environmental stress precipitated severe pathological injury and robust inflammatory in the intestinal mucosa, characterized by a multifold upregulation of Th1/Th2-related cytokines and the suppressed expression of Ocln, ZO-1, pIgR, and SIgA. Further experiments revealed that the humid heat environment exacerbated neurological deficits in influenza A virus-infected mice, accompanied by a significant reduction in neurotransmitter levels. Conclusions: These data demonstrate that exposure to a humid heat environment exacerbates influenza infection severity through the dysregulation of the intestinal homeostasis and the neuroendocrine system, revealing the potential mechanisms underlying the digestive and nervous system symptoms observed in influenza patients.PMID:41561482 | PMC:PMC12813360 | DOI:10.1016/j.bbih.2025.101164

Cureus. 2025 Dec 19;17(12):e99600. doi: 10.7759/cureus.99600. eCollection 2025 Dec.ABSTRACTBackground Host genetics, gut microbiota, and metabolites have each been independently linked to allergic diseases such as asthma, allergic rhinitis, and eczema. However, the complex interactions between these three components remain poorly understood, largely due to a reliance on single-omics analyses. Integrating multi-omics data is essential for uncovering the underlying mechanisms of allergic disease pathogenesis. Methodology We performed a systematic, integrative analysis of large-scale public data from gut microbiome genome-wide association studies (GWAS) and blood metabolome-GWAS. We retrieved data from studies with cohorts of over 400 subjects. Overlapping genetic loci were identified by cross-referencing significant associations (p<1×10⁻⁶ for gene-microbe and p<1×10⁻⁵ for gene-metabolite) to define gene-microbe-metabolite trios. These trios were then cross-referenced with relevant databases (e.g., GWAS Catalog, gutMDisorder, and Human Metabolome Database (HMDB)) to establish their potential link to allergic diseases. Results Our integrative approach identified 12 distinct gene-gut microbiota-blood metabolite trios associated with allergic diseases. Established patterns were confirmed, including the ABO gene's influence on Bifidobacterium bifidum, which is known to impact immune regulation. Novel associations were also uncovered, including structural genes (e.g., LAMA2, PTPRT) potentially facilitating microbiota attachment and modulating metabolites such as octadecanedioate and genes involved in neurotransmitter signaling (e.g., SYN3, PDE1A), suggesting potential neuro-immune mechanisms. Conclusions By integrating microbiome-GWAS and metabolome-GWAS data, we have generated a valuable resource of candidate pathways underlying allergic disease pathogenesis. The identified trios provide specific, testable hypotheses for future validation studies and potential targets for biomarker discovery. This work underscores the power of multi-omics integration in allergy research and provides a clear roadmap for investigating complex gene-environment interactions.PMID:41561239 | PMC:PMC12813944 | DOI:10.7759/cureus.99600

Front Nutr. 2026 Jan 5;12:1685003. doi: 10.3389/fnut.2025.1685003. eCollection 2025.ABSTRACTBACKGROUND/OBJECTIVES: Policosanol, a bioactive compound derived from rice bran wax, has demonstrated potential for alleviating stress, yet its underlying mechanisms remain elusive. This study aimed to elucidate its role in mitigating chronic stress-induced growth impairment and to explore its interactions with the gut microbiota and metabolomics.METHODS: Male rats were subjected to a 4-week chronic restraint stress protocol with or without policosanol supplementation (2 mg/kg/day). Systemic responses were evaluated by measuring growth parameters (including weight gain and muscle mass), serum biomarkers [cortisol and catecholamines (CA)], 16S rRNA sequencing (for cecal microbiota analysis), and LC-MS metabolomics (for cecal metabolite profiling).RESULTS: Stress induced a significant reduction in weight gain (-11.0%, p < 0.05) and a marked elevation of serum cortisol (+86.2%) and CA (+88.3%, both p < 0.05). Policosanol treatment restored weight gain to 85.5% of control levels (p < 0.05) and reduced cortisol and catecholamine levels by 29.5% and 26.8%, respectively (both p < 0.05). Stress-induced alterations in gut microbiota included a 4.1-fold increase in p_Verrucomicrobiota and a 3.8-fold increase in g_Akkermansia, along with metabolite changes such as a 4.2-fold elevation in Proscillaridin and a 65% decrease in Phenylacetylglutamine (PAGln) (both p < 0.05). Policosanol supplementation normalized gut microbiota composition (p_Verrucomicrobiota decreased by 36%, p < 0.05) and restored metabolite levels (PAGln increased by 80%, p < 0.01). Negative correlations were observed between g_Akkermansia abundance and weight gain (p < 0.01), while PAGln positively correlated with growth (p < 0.05) and negatively correlated with GSH-Px (p < 0.001), cortisol (p < 0.001), and CA (p < 0.001). Moreover, the g_Bacteroides-PAGln axis exhibited a strong interaction (p < 0.001).CONCLUSION: Policosanol mitigates stress-induced growth impairment by modulating gut microbiota (e.g., reducing p_Verrucomicrobiota and g_Akkermansia abundances) and restoring metabolite levels (e.g., increasing PAGln). The coregulation of the gut microbiota and metabolome was highlighted by a strong correlation between g_Bacteroides and Phenylacetylglutamine (PAGln), suggesting a potential functional interaction that may contribute to the anti-stress effects of policosanol, though causality remains to be established.PMID:41561167 | PMC:PMC12812650 | DOI:10.3389/fnut.2025.1685003

Biomed Rep. 2026 Jan 2;24(2):28. doi: 10.3892/br.2026.2101. eCollection 2026 Feb.ABSTRACTRefractory ascites is a serious complication of decompensated cirrhosis, yet its intestinal microbial and metabolic characteristics remain incompletely understood. The present study combined 16S rRNA sequencing and gas chromatography-mass spectrometry-based untargeted metabolomics to investigate the gut microbial composition and metabolite profiles of 70 patients with refractory ascites due to cirrhosis (OB group) and 70 healthy individuals (NC group). Analyses included microbial diversity evaluation, taxonomic comparison, functional prediction, metabolite screening and disease association mapping. Compared with the NC group, the OB group showed reduced α diversity and distinct β diversity patterns, with enrichment of Proteobacteria and a reduction in anaerobic and Gram-positive taxa. BugBase analysis indicated increased proportions of potentially pathogenic, biofilm-forming and oxidative stress-tolerant phenotypes. LEfSe analysis further revealed group-specific taxa, such as enrichment of Bacteroidota and Actinobacteriota in the NC group and Firmicutes-related genera including Clostridium and Lactobacillus in the OB group. Functional predictions suggested group differences in carbohydrate and lipid metabolism, membrane transport and vitamin-related pathways. Metabolomic analysis identified 2,890 altered metabolites and Kyoto Encyclopedia of Genes and Genomes enrichment highlighted an involvement in serotonergic synapse and steroid hormone biosynthesis. Receiver operator characteristic curve analysis revealed a good discriminatory performance (area under the curve >0.93) for 10 selected metabolites. Several of these metabolites, including L-tryptophan and hypoxanthine, were further linked to inflammatory, neurodegenerative and neoplastic diseases. In conclusion, patients with refractory ascites exhibited notable structural and functional alterations in gut microbiota and metabolism. These findings provide insights into the gut-liver axis in cirrhosis and may inform future research on microbial or metabolic biomarkers.PMID:41561140 | PMC:PMC12814326 | DOI:10.3892/br.2026.2101