PubMed
UPLC-QTOF-MS-based metabolomics and chemometrics studies of geographically diverse C. torulosa needles
Anal Methods. 2025 Feb 10. doi: 10.1039/d4ay01654h. Online ahead of print.ABSTRACTCupressus torulosa, an evergreen tree commonly known as the Himalayan or Bhutan cypress, is a significant coniferous species native to the Himalayan regions of Bhutan, northern India, Nepal, and Tibet. In this study, we employed ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) integrated with chemometrics to analyze the metabolite profiles of C. torulosa needles collected from 14 distinct geographical regions. Advanced statistical tools, including Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA), were utilized to identify significant variations in the chemical composition across these locations. Our analysis identified 24 marker compounds consistently present in all samples, screened using stringent filtering criteria including One-way ANOVA, moderated T-test, and multiple testing correction with the Benjamini-Hochberg FDR method. Additionally, for the first time, we established the flavonoid biosynthesis pathway in C. torulosa, enhancing the understanding of its metabolic fingerprint. These findings provide critical insights into the phytochemical diversity of C. torulosa and offer valuable tools for quality control, authentication and advancing the application of UPLC-QTOF-MS in natural product research.PMID:39927411 | DOI:10.1039/d4ay01654h
Effects of <em>Salmonella Typhimurium</em> infection on intestinal flora and intestinal tissue arachidonic acid metabolism in Wenchang chickens
Front Microbiol. 2025 Jan 24;16:1514115. doi: 10.3389/fmicb.2025.1514115. eCollection 2025.ABSTRACTSalmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether arachidonic acid (ARA) metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and ARA metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), lipoxin A4 (LXA4), ± 8(9)-EET, ± 11(12)-EET, and ± 8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (Phospholipase A2 PLA2 and Cyclooxygenase-2 COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including Interferon-γ (IFN-γ), Transforming growth factor-β1 (TGF-β1), Interleukin-4 (IL-4), and Interleukin-6 (IL-6). In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. The present study revealed the structure of cecal flora in S. Typhimurium-infected Wenchang chickens. In addition, this study demonstrated that S. Typhimurium activates the ARA cyclooxygenase metabolic pathway, which in turn mediates the development of intestinal inflammation in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.PMID:39927263 | PMC:PMC11803450 | DOI:10.3389/fmicb.2025.1514115
Association between liver fibrosis and osteoporosis in adults aged 50 and older: insights from the Bushehr Elderly Health Program
J Diabetes Metab Disord. 2025 Feb 6;24(1):65. doi: 10.1007/s40200-025-01574-z. eCollection 2025 Jun.ABSTRACTOBJECTIVES: Both liver fibrosis and osteoporosis share inflammatory pathways, with liver fibrosis potentially contributing to decreased bone mineral density (BMD). The rising prevalence of non-alcoholic fatty liver disease (NAFLD) and associated liver fibrosis, especially in older populations, may increase the risk of osteoporosis, but evidence remains inconclusive. This study aims to investigate the relationship between liver fibrosis and osteoporosis in individuals over 50 years old.METHODS: This cross-sectional study used data from the Bushehr Elderly Health Program (BEHP), a cohort of 2,000 participants aged 50 and older, selected through multistage stratified random sampling. BMD and trabecular bone score (TBS) measurements were assessed. The Fibrosis-4 (FIB-4) index, a surrogate marker for liver fibrosis, was also calculated to examine its association with these bone health indicators. Multiple linear regression was applied to assess the relationship between FIB-4 and lumbar, hip, femoral neck BMD, and TBS scores, while logistic regression was used to evaluate osteoporosis as the dependent variable.RESULTS: A total of 1,959 participants with adequate data were included in our analysis. 538 participants had osteoporosis, 936 participants had osteopenia, and 485 participants had normal bone density. FIB-4 index was higher in osteoporotic groups (1.45 ± 0.90) than in osteopenic (1.26 ± 0.58, p < 0.001) and normal groups (1.17 ± 0.48, p < 0.001). After controlling for confounders, FIB-4 index was negatively associated with hip BMD (βmen=-0.0162; 95% CI: -0.0313, -0.0012 and βwomen=-0.0221; 95% CI: -0.0340, -0.0102), femoral neck BMD (βmen=-0.0216; 95% CI: -0.0356, -0.0076 and βwomen=-0.0233; 95% CI: -0.0342, 0.0124), and TBS (βmen=-0.0154; 95% CI: -0.0264, -0.0043 and βwomen=-0.0244; 95% CI: -0.0338, -0.0149) in both genders and with lumbar BMD in women (β=-0.0176; 95% CI: -0.0307, -0.0045). An increase in the FIB-4 index was associated with more than a twofold rise in the risk of developing osteoporosis in women (OR = 2.123; 95% CI: 1.503, 3.000; p < 0.001) and a 36% higher risk in men (OR = 1.366; 95% CI: 1.012, 1.844; p = 0.042).CONCLUSIONS: Liver fibrosis is associated with decreased bone density and attenuated bone architecture. Elevated FIB-4 index has been identified as a risk factor for osteoporosis, indicating a potential link between liver fibrosis and deteriorating bone health.PMID:39927178 | PMC:PMC11803014 | DOI:10.1007/s40200-025-01574-z
Studies on the alleviating effect of <em>Bifidobacterium lactis</em> V9 on dextran sodium sulfate-induced colitis in mice
Front Med (Lausanne). 2025 Jan 24;12:1496023. doi: 10.3389/fmed.2025.1496023. eCollection 2025.ABSTRACTBACKGROUND: Inflammatory bowel disease (IBD) has become a global public health problem with complex pathogenesis and limited therapeutic options. We aimed to investigate the potential mechanisms by which Bifidobacterium lactis V9 (V9) alleviated colitis in a dextran sodium sulfate-induced colitis model mice.METHODS: Mice were induced to develop colitis by drinking DSS solution to induce colitis. The expression of the relevant factors in the blood supernatant of the mice was determined by ELISA. RT-qPCR and Western blotting were used to detect mRNA and protein expression of target genes. The fecal microbiota was analyzed by 16S rRNA sequencing. Intestinal metabolites were analyzed by untargeted metabolomics.RESULTS: V9 effectively improved the overall symptoms of the colitis model mice. H&E showed that V9 re-stored the intestinal tissue structure. ELISA showed that V9 decreased the levels of IL-6, IL-22, and TNF-α and increased IL-10, SP, VIP, and 5-HT. V9 increased the expression of AHR, CYP1A1, MUC2, Claudin-3, Occludin, and ZO-1, and decreased 5-hydroxytryptamine transporter and Claudin-2. V9 increased the abundance of gut microbiota in colitis mice to promote the growth of beneficial bacteria. V9 increased tryptophan metabolites, and short-chain fatty acids, and improved gut inflammation.CONCLUSION: V9 attenuates intestinal inflammation, improves the mucosal barrier, modulates intestinal microecology and exerts a protective effect in a mouse model of DSS-induced colitis.PMID:39926427 | PMC:PMC11802548 | DOI:10.3389/fmed.2025.1496023
Biocontrol efficacy of native <em>Metarhizium rileyi</em> (Hypocreales: Clavicipitaceae) isolates against <em>Spodoptera litura</em> (F) (Lepidoptera: Noctuidae) and in silico effect of the secondary metabolites against the virulent proteins of the insect
3 Biotech. 2025 Mar;15(3):57. doi: 10.1007/s13205-025-04226-4. Epub 2025 Feb 7.ABSTRACTThis study explores the insecticidal potential of secondary metabolites derived from Metarhizium rileyi against Spodoptera litura through an integrative approach involving genomics, metabolomics, and bioinformatics. Four native isolates of M. rileyi were identified and characterized for their insecticidal efficacy. Among these, the SlMr-DOR isolate exhibited the highest effectiveness, achieving a remarkable 90.0% mortality in laboratory bioassays and 93.3% mortality when tested with its crude extract. Gas chromatography-mass spectrometry (GC-MS) analysis of the SlMr-DOR isolate revealed a diverse profile of bioactive volatile secondary metabolites, including squalene, diethyl phthalate, 4-anilinoquinazoline, vinyl 2-ethylhexanoate, 2-phenyl-3-formyl-pyrrole, chloramphenicol, hentriacontane, phthalic acid derivatives, pentacosane, nonanamide, and eicosanoic acid. Among these metabolites, commercially available squalene and diethyl phthalate were further validated for their insecticidal activity through bioassay studies. Molecular docking analysis demonstrated the strong binding affinity of these metabolites with key S. litura target proteins, including putative chemosensory protein CSP8 and α-amylase, revealing their potential mode of action. The results establish that the secondary metabolites, particularly from the SlMr-DOR isolate, are highly effective against S. litura. This study emphasizes the potential of such metabolites as sustainable and effective alternatives for pest management strategies, contributing to integrated pest control approaches and reducing reliance on synthetic chemical pesticides.PMID:39926106 | PMC:PMC11806170 | DOI:10.1007/s13205-025-04226-4
The Era of Preemptive Medicine: Developing Medical Digital Twins through Omics, IoT, and AI Integration
JMA J. 2025 Jan 15;8(1):1-10. doi: 10.31662/jmaj.2024-0213. Epub 2024 Nov 11.ABSTRACTPreemptive medicine represents a paradigm shift from reactive treatment to proactive disease prevention. The integration of omics technologies, the Internet of Things (IoT), and artificial intelligence (AI) has facilitated the development of personalized, predictive, and preemptive healthcare strategies. Omic technologies, such as genomics, proteomics, and metabolomics, provide comprehensive insights into molecular profile of an individual, revealing potential disease predispositions and health trajectories. IoT devices, such as wearables and smartphones, enable continuous and periodic monitoring of physiological parameters, thus providing a dynamic view of an individual's health status. AI algorithms analyze comprehensive and complex data from omics and IoT technologies to identify patterns and correlations that inform predictive models of disease risk, progression, and response to interventions. Medical digital twins, or virtual replicas of an individual's biological processes, have emerged as the cornerstone of preemptive medicine. The integration of omics, IoT, and AI enables the development of medical digital twins, which in turn allows for precise simulation of human physiological profiles, prediction of future health outcomes, and virtual individual clinical trials, facilitating personalized proactive interventions and preemptive disease control. This review demonstrates the convergence of omics, IoT, and AI in preemptive medicine, highlighting their potential to revolutionize healthcare by enabling early disease detection, personalized treatment strategies, and chronic disease prevention. We show how AI leverages omics and IoT in preemptive medicine through several case studies while also discussing the necessary data for developing medical digital twins and addressing ethical and social aspects that warrant consideration. Medical digital twins signify a fundamental transformation in health management, shifting from treating diseases after their occurrence to controlling them before their occurrence. This approach enhances the effectiveness of medical interventions and improves overall health outcomes, preparing for a healthier future.PMID:39926086 | PMC:PMC11799569 | DOI:10.31662/jmaj.2024-0213
Fucoidan alleviated colitis aggravated by fiber deficiency through protecting the gut barrier, suppressing the MAPK/NF-κB pathway, and modulating gut microbiota and metabolites
Front Nutr. 2025 Jan 24;11:1462584. doi: 10.3389/fnut.2024.1462584. eCollection 2024.ABSTRACTInsufficient dietary fiber intake has become a global public health issue, affecting the development and management of various diseases, including intestinal diseases and obesity. This study showed that dietary fiber deficiency enhanced the susceptibility of mice to colitis, which could be attributed to the disruption of the gut barrier integrity, activation of the NF-κB pathway, and oxidative stress. Undaria pinnatifida fucoidan (UPF) alleviated colitis symptoms in mice that fed with a fiber deficient diet (FD), characterized by increased weight gain and reduced disease activity index, liver and spleen indexes, and histological score. The protective effect of UPF against FD-exacerbated colitis can be attributed to the alleviation of oxidative stress, the preservation of the gut barrier integrity, and inhibition of the MAPK/NF-κB pathway. UPF ameliorated the gut microbiota composition, leading to increased microbiota richness, as well as increased levels of Muribaculaceae, Lactobacillaceae, and Bifidobacterium and reduced levels of Proteobacteria, Bacteroidetes, and Bacteroides. Metabolomics analysis revealed that UPF improved the profile of microbiota metabolites, with increased levels of carnitine and taurine and decreased levels of tyrosine and deoxycholic acid. This study suggests that UPF has the potential to be developed as a novel prebiotic agent to enhance human health.PMID:39925971 | PMC:PMC11802440 | DOI:10.3389/fnut.2024.1462584
Disruption of Gut Microbiota and Associated Fecal Metabolites in Collagen-Induced Arthritis Mice During the Early Stage
J Inflamm Res. 2025 Feb 4;18:1703-1717. doi: 10.2147/JIR.S502980. eCollection 2025.ABSTRACTBACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease and increasing evidence suggests that disturbances in the composition and function of gut microbiota are potentially implicated in the progression of RA. Further revealing the microbiota and related metabolic disorders in the preclinical stage of RA (pre-RA) is of great significance for exploration of disease mechanisms.METHODS: DBA/1 mice were injected with type II collagen on days 0 and 21 to establish collagen-induced arthritis (CIA) mouse model. Footpad thickness, serum autoantibodies, and joint histopathology were used to assess the progression of RA. A combination of 16S rRNA sequencing, untargeted metabolomics and targeted short-chain fatty acids (SCFAs) analysis were employed to comprehensively investigate the alterations of gut microbiota and fecal metabolites in CIA during the pre-RA stage.RESULTS: 20 days after the initial collagen immunization, CIA mice showed immune responses without joint symptoms, alongside gut microbiota disruption. Alterations were observed in 20 microbial taxa, including Oscillospira, Bifidobacterium, Ruminococcus, Allobaculum, Alistipes, Lactobacillus, and Candidatus_Arthromitus, etc. Untargeted and targeted metabolomics identified 33 altered fecal metabolites, mainly including sugars and their derivatives, amino acids, long-chain fatty acids and SCFAs, etc. Correlation analysis showed significant correlations between specific gut microbial abundances and fecal metabolite levels. Especially, SCFAs were strongly associated with Bifidobacterium, Alistipes, Ruminococcus, Anaerotruncus, and Allobaculum.CONCLUSION: These findings suggest that collagen immunization leads to disruption of gut microbiome and induces changes of fecal metabolites in mice, which may play a key role in early development of RA in CIA mice.PMID:39925933 | PMC:PMC11806705 | DOI:10.2147/JIR.S502980
Plasma GLP-1 and metabolic dynamics during human liver regeneration and their association with posthepatectomy liver failure
Hepatobiliary Surg Nutr. 2025 Feb 1;14(1):49-65. doi: 10.21037/hbsn-24-464. Epub 2025 Jan 17.ABSTRACTBACKGROUND: Metabolic regulation is critical during liver regeneration in rodents, but human data are limited. We investigated perioperative dynamics of circulating metabolites and plasma levels of glucagon-like peptide-1 (GLP-1) and GLP-2, in patients undergoing liver resections, exploring their associations with the histological phenotype of metabolic dysfunction-associated steatotic liver disease (MASLD) and posthepatectomy liver failure (PHLF).METHODS: Eighty-one and 75 patients from two centers between 2012 and 2023 were studied. Targeted quantitative metabolomic assay of 180 circulating metabolites, perioperative GLP-1, GLP-2, and standard lipid parameter level evaluation was employed. An exploratory PHLF prediction model was developed, including GLP-1 as a metabolic parameter.RESULTS: Significant alterations of 44 metabolites by postoperative day (POD) 1 and 40 by POD5 were observed, mainly among phospholipid species. Unsupervised clustering identified two metabolic clusters, with one encompassing 93% of PHLF patients by POD5 (P<0.001). Standard plasma lipid parameters displayed consistent decrease after hepatectomy, independent from MASLD phenotype, with the lowest levels in PHLF patients. Postoperative GLP-1 and GLP-2 dynamics displayed a reciprocal pattern, indicating adaptive change in secretion. Preoperative GLP-1 levels were significantly increased in PHLF (P=0.02). Furthermore, incorporation of GLP-1 into the established aspartate aminotransferase to platelet ratio index (APRI) + albumin-bilirubin (ALBI) score, improved PHLF prediction [area under the curve (AUC): 0.833, 95% confidence interval (CI): 0.660-0.964].CONCLUSIONS: Significant metabolic changes occur during human liver resection, particularly in phospholipid metabolism, along with distinct perioperative dynamics of GLP-1 and GLP-2, closely linked to PHLF and independent of the histological phenotype of MASLD. Additionally, we provide exploratory results on the predictive value of GLP-1 for PHLF, emphasizing a holistic model of liver function assessment highlighting the metabolic component of human liver regeneration.PMID:39925909 | PMC:PMC11806138 | DOI:10.21037/hbsn-24-464
The gut-liver axis links the associations between serum carotenoids and non-alcoholic fatty liver in a 7.8-year prospective study
Hepatobiliary Surg Nutr. 2025 Feb 1;14(1):16-32. doi: 10.21037/hbsn-23-526. Epub 2024 Jul 15.ABSTRACTBACKGROUND: Many studies have shown that carotenoids are beneficial to non-alcoholic fatty liver disease (NAFLD). Therefore, we explored potential biomarkers of gut microbiota and fecal and serum metabolites linking the association between serum carotenoids and NAFLD in adults.METHODS: This 7.8-year prospective study included 2921 participants with serum carotenoids at baseline and determined NAFLD by ultrasonography (ULS-NAFLD) every 3 years. A total of 828 subjects additionally underwent magnetic resonance imaging to identify NAFLD (MRI-NAFLD). Gut microbiota was analyzed by 16S rRNA sequencing in 1,661 participants, and targeted metabolomics profiling in 893 feces and 896 serum samples was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in the middle term.RESULTS: A total of 2,522 participants finished follow-up visits. Of these participants, 770, 301, 474, and 977 were categorized into NAFLD-free, improved, new-onset, and persistent NAFLD groups based on their ULS-NAFLD status changes, respectively, and 342/828 were MRI-verified NALFD. Longitudinal analyses showed an inverse association between carotenoids and NALFD risk/presence (P-trend <0.05). Multivariable-adjusted odds ratios (ORs)/hazard ratio (HR) [95% confidence intervals (CIs)] of NAFLD for quartile 4 (vs. quartile 1) of total carotenoids were 0.63 (0.50, 0.80) for incident ULS-NAFLD, 0.20 (0.15, 0.27) for persistent ULS-NAFLD, 1.53 (1.10, 2.12) for improved-NAFLD, and 0.58 (0.39, 0.87) for MRI-NAFLD. The biomarkers in the gut-liver axis significantly associated with both serum carotenoids and NAFLD included sixteen microbial genera mainly in Ruminococcaceae and Veillonellaceae family, nineteen fecal metabolites containing medium-chain fatty acids (MCFAs), bile acids, and carnitines, and sixteen serum metabolites belonging to organic acids and amino acids. The total carotenoids-related scores of significant microbial genera, fecal and serum metabolites mediated the carotenoids-NAFLD association by 8.72%, 12.30%, and 16.83% (all P<0.05) for persistent NAFLD and 9.46%, 8.74%, and 15.7% for incident-NAFLD, respectively.CONCLUSIONS: Our study reveals a beneficial association of serum carotenoids and incident and persistent NAFLD. The identified gut-liver axis biomarkers provided mechanistic linkage for the epidemiological association.PMID:39925899 | PMC:PMC11806141 | DOI:10.21037/hbsn-23-526
The impact of different gastrointestinal reconstruction techniques on gut microbiota after gastric cancer surgery
Front Microbiol. 2025 Jan 24;15:1494049. doi: 10.3389/fmicb.2024.1494049. eCollection 2024.ABSTRACTINTRODUCTION: Gastric cancer is one of the common malignant tumors in the digestive tract, characterized by high incidence and mortality rates. This is particularly significant in China, where a large proportion of global new cases of gastric cancer and related deaths occur. In recent years, with the continuous development of molecular biology technology, people have gained a deeper understanding of the gastrointestinal microbiome, and studies have shown that it is closely related to the occurrence, development, and therapeutic response of gastric cancer. Although surgical intervention is crucial in significantly extending the survival of gastric cancer patients, the disruption of the balance of the intestinal microbiota caused by surgery itself should not be overlooked, as it may affect postoperative recovery.METHODS: This study was approved by the Biomedical Ethics Committee of Sichuan Mianyang 404 Hospital. A random sampling method was used to select patients who underwent gastric cancer surgery at the hospital from January 2023 to December 2023. All patients signed written informed consent forms. Standardized perioperative management was conducted for the patients in the study, including preoperative preparation, intraoperative handling, and postoperative treatment. Fecal samples were collected from patients before surgery (before bowel preparation) and around one week after surgery for 16S rRNA sequencing analysis, through which differential biomarkers and related functional genes were sought.RESULTS: The study results indicated that there was no significant difference in the diversity of the gut microbiota between the two groups. Compared with the R-Y group, the DTR surgical method significantly altered the structure of the gut microbiota, affecting the types, quantities, and proportions of intestinal bacteria. Furthermore, the DTR group exhibited poorer postoperative nutritional absorption capacity compared to the R-Y group, as indicated by a lower F/B ratio. The R-Y group showed a richer abundance of Bacteroidetes and a lower abundance of Proteobacteria, as well as a higher F/B ratio after surgery. These findings provide new insights into the changes in the gut microbiota following gastric cancer surgery, which may be of significant importance for postoperative recovery and long-term health management.DISCUSSION: This study reveals the impact of different gastrointestinal reconstruction techniques on the postoperative gut microbiota of gastric cancer patients, providing new insights into the physiological changes during the postoperative recovery period. Although there was no significant difference in microbial diversity between the DTR group and the R-Y group, the DTR group showed more pronounced changes in microbial structure postoperatively, which may be associated with an increased risk of postoperative infection. These findings emphasize the importance of considering the impact on the gut microbiota when selecting gastric cancer surgery methods. However, the study had a limited sample size and did not delve into changes in metabolites. Future studies should expand the sample size and conduct metabolomic analyses to further validate these preliminary findings.PMID:39925886 | PMC:PMC11804259 | DOI:10.3389/fmicb.2024.1494049
Metagenomic Sequencing Combined with Metabolomics to Explore Gut Microbiota and Metabolic Changes in Mice with Acute Myocardial Infarction and the Potential Mechanism of Allicin
Drug Des Devel Ther. 2025 Feb 3;19:771-791. doi: 10.2147/DDDT.S504884. eCollection 2025.ABSTRACTBACKGROUND: Acute myocardial infarction (AMI) is a significant contributor to global morbidity and mortality. Allicin exhibits promising therapeutic potential in AMI as a primary bioactive component derived from garlic; however, its underlying mechanisms remain incompletely elucidated.METHODS: Our study induced AMI in mice by ligating the left coronary artery, and administered allicin orally for 28 days. The cardioprotective effects of allicin treatment were comprehensively assessed using echocardiography, histopathological examinations, intestinal barrier function, and serum inflammatory factors. The potential mechanisms of allicin were elucidated through analysis of metagenomics and serum metabolomics. Network pharmacology (NP) was used to further investigate and validate the possible molecular mechanisms of allicin.RESULTS: Our findings revealed allicin's capacity to ameliorate cardiac impairments, improve intestinal barrier integrity, and reduce serum IL-18 and IL-1β levels after AMI. Further analysis demonstrated that the administration of allicin has the potential to ameliorate intestinal flora disorder following AMI by modulating the abundance of beneficial bacteria, such as g_Lactobacillus, g_Prevotella, g_Alistipes, and g_Limosilactobacillus, while reducing the abundance of harmful bacteria g_Parasutterella. Additionally, it exhibits the ability to enhance myocardial energy metabolism flexibility through modulating metabolites and key enzymes associated with the fatty acid metabolic pathway. Mechanistically, NP and in vivo experiments indicated that allicin might suppress pyroptosis and reduce inflammatory response via blocked activation of the NF-κB-mediated NLRP3/Caspase-1/GSDMD pathway. Moreover, Spearman correlation analysis suggested a significant association between the allicin-induced alterations in microbiota and metabolites with cardiac function and inflammatory cytokines.CONCLUSION: Our study demonstrated that allicin alleviated myocardial injury and reduced inflammatory response by inhibiting the NF-κB-mediated NLRP3/Caspase-1/GSDMD pathway while remodeling microbiota disturbance, improving serum metabolic disorder, and enhancing the intestinal barrier. These research findings offer a novel perspective on the potential therapeutic value of allicin as an adjunctive dietary supplement to conventional treatments for AMI.PMID:39925879 | PMC:PMC11806679 | DOI:10.2147/DDDT.S504884
DPANN symbiont of <em>Haloferax volcanii</em> accelerates xylan degradation by the non-host haloarchaeon <em>Halorhabdus</em> sp
iScience. 2025 Jan 4;28(2):111749. doi: 10.1016/j.isci.2025.111749. eCollection 2025 Feb 21.ABSTRACTThis study examines a natural consortium of halophilic archaea, comprising xylan-degrading Halorhabdus sp. SVX81, consortium cohabitant Haloferax volcanii SVX82 (formerly H. lucentense SVX82), and its DPANN ectosymbiont Ca. Nanohalococcus occultus SVXNc. Transcriptomics and targeted metabolomics demonstrated that the tripartite consortium outperformed individual and the Halorhabdus sp. SVX81 with H. volcanii SVX82 bipartite cultures in xylan degradation, exhibiting a division of labor: the DPANN symbiont processed glycolysis products, while other members performed xylan depolymerization and biosynthesis of essential compounds. Electron microscopy and cryo-electron tomography revealed the formation of heterocellular biofilms interlinked by DPANN cells. The findings demonstrated that DPANN symbionts can interact directly with other members of microbial communities, which are not their primary hosts, influencing their gene expression. However, DPANN proliferation requires their primary host presence. The study highlights the collective contribution of consortium members to xylan degradation and their potential for biotechnological applications in the management of hypersaline environments.PMID:39925428 | PMC:PMC11803251 | DOI:10.1016/j.isci.2025.111749
Leaf Beetle Symbiotic Bacteria Degrade Chlorogenic Acid of Poplar Induced by Egg Deposition to Enhance Larval Survival
Plant Cell Environ. 2025 Feb 10. doi: 10.1111/pce.15427. Online ahead of print.ABSTRACTInsect symbiotic microbiota acting as a third-party force of plant-insect interactions, play a significant role in insect hosts tolerance to phytochemical defences. However, it remains unknown whether insect symbiotic bacteria can assist the host in degrading phytochemical defences induced by egg deposition. Plagiodera versicolora is a worldwide forest pest. Our study showed that P. versicolora egg deposition on Populus davidiana × Populus bolleana induced significant changes in the transcriptome and metabolome of leaves. Combined qRT-PCR and LC-MS quantitative analysis of metabolic pathways showed that the contents of chlorogenic acid and rutin were significantly increased upon egg deposition in poplar. Bioassays indicated that the high concentration of chlorogenic acid induced by egg deposition could significantly reduce the performance of germ-free larvae. Six symbiotic bacterial strains with potential ability to degrade chlorogenic acid were isolated and identified. Their degradation products did not affect larval survival either. In vivo inoculation assays showed that four of those symbiotic bacteria could assist in the degradation of high concentration of chlorogenic acid induced by egg deposition and improve the larval survival. Our study provides clear evidence that the insect symbiotic bacteria can mediate the tolerance of herbivorous insects against plant toxins induced by egg deposition.PMID:39925102 | DOI:10.1111/pce.15427
Development of an Oxylipin Library Using Liquid Chromatography-Ion Mobility Quadrupole Time-of-Flight: Application to Mouse Brain Tissue
Anal Chem. 2025 Feb 9. doi: 10.1021/acs.analchem.4c06265. Online ahead of print.ABSTRACTOxylipins are bioactive lipid mediators derived from polyunsaturated fatty acids (PUFAs) that play crucial roles in physiological and pathological processes. The analysis and identification of oxylipins are challenging due to the numerous isomeric forms. Ion mobility (IM), which separates ions based on their spatial configuration, combined with liquid chromatography (LC) and mass spectrometry (MS), has been proven effective for separating isomeric compounds. In this study, we developed an extensive oxylipin library containing information on retention time (RT), m/z, and CCS values for 74 oxylipin standards using LC-IM-QTOF-MS in positive and negative ionization modes. The oxylipins in the library were grouped into 15 isomer categories to evaluate the efficacy of IM in isomeric separation. Various adducts were investigated, including protonated, deprotonated, and sodiated forms. The ΔCCS% for more than 1000 isomeric pairs was calculated, revealing that 30% of these exhibited a ΔCCS% greater than 2%. Positive ionization mode demonstrated superior separation capabilities, with 274 isomer pairs achieving baseline separation (ΔCCS% > 4%). Sodium adducts significantly improved isomer separation. With the inclusion of LC separation, only nine oxylipins coeluted, forming six different isomeric pairs. CCS values for the adducts [M+Na]+ and [M+2Na-H]+ separated three of these isomeric pairs. The CCS values were compared to experimental libraries, confirming the high reproducibility of CCS measurements, with average errors below 2%. Applying this library to mouse brain samples, 19 different oxylipins were identified by matching RT, m/z, and CCS values. Coeluting isomers, 9- and 13-HODE, 8- and 12-HETE, and 15-oxo-ETE and 14(15)-EpETrE, were successfully separated and identified using drift time separation.PMID:39924946 | DOI:10.1021/acs.analchem.4c06265
Longevity Humans Have Youthful Erythrocyte Function and Metabolic Signatures
Aging Cell. 2025 Feb 9:e14482. doi: 10.1111/acel.14482. Online ahead of print.ABSTRACTLongevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging-related diseases. It has long been speculated that "rejuvenation molecules" exist in their blood to promote extended lifespan. We unexpectedly discovered that longevity individuals exhibit erythrocyte oxygen release function similar to young individuals, whereas most elderly show reduced oxygen release capacity. Untargeted erythrocyte metabolomics profiling revealed that longevity individuals are characterized by youth-like metabolic reprogramming and these metabolites effectively differentiate the longevity from the elderly. Quantification analyses led us to identify multiple novel longevity-related metabolites within erythrocytes including adenosine, sphingosine-1-phosphate (S1P), and glutathione (GSH) related amino acids. Mechanistically, we revealed that increased bisphosphoglycerate mutase (BPGM) and reduced MFSD2B protein levels in the erythrocytes of longevity individuals collaboratively work together to induce elevation of intracellular S1P, promote the release of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from membrane to the cytosol, and thereby orchestrate glucose metabolic reprogramming toward Rapoport-Luebering Shunt to induce the 2,3-BPG production and trigger oxygen delivery. Furthermore, increased glutamine and glutamate transporter expression coupled with the enhanced intracellular metabolism underlie the elevated GSH production and the higher anti-oxidative stress capacity in the erythrocytes of longevity individuals. As such, longevity individuals displayed less systemic hypoxia-related metabolites and more antioxidative and anti-inflammatory metabolites in the plasma, thereby healthier clinical outcomes including lower inflammation parameters as well as better glucose-lipid metabolism, and liver and kidney function. Overall, we identified that youthful erythrocyte function and metabolism enable longevity individuals to better counteract peripheral tissue hypoxia, inflammation, and oxidative stress, thus maintaining healthspan.PMID:39924931 | DOI:10.1111/acel.14482
Metabolomics Reveal the Anti-Hyperuricemia Effects and Mechanisms of Sunflower Head Extract in Hyperuricemia Mice Model
Mol Nutr Food Res. 2025 Feb 9:e202401017. doi: 10.1002/mnfr.202401017. Online ahead of print.ABSTRACTHyperuricemia (HUA) is a globally prevalent metabolic disease characterized by excessive production or insufficient excretion of uric acid in the serum. Although several drugs are available for the treatment of HUA, they have been associated with undesirable side effects. Therefore, this study aims to evaluate the therapeutic effects of sunflower head extract (KHE) on HUA in a mouse model and explore its potential mechanisms. All mice were randomly divided into three groups: Normal control (NC, 0.5% CMC-Na), HUA model (MD, yeast extract paste 20 g/kg), and KHE treatment group (KHE, 1 g/kg). Biochemical indicators, the oxidative stress state, and metabolomics were analyzed. KHE reduced the levels of 5-aminoimidazole ribonucleotide, xanthine, hypoxanthine, and uric acid in the serum of mice with HUA but increased the levels of adenine and taurine. KHE decreased the activities of superoxide dismutase (SOD) enzymes, the hepatic hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels, and the serum levels of betaine aldehyde and beta-D-glucosamine. KHE improved oxidative stress levels and mitigated potential damage to the kidneys and joints caused by urate deposition. These findings provide comprehensive evidence supporting the anti-HUA effects and underlying mechanisms of KHE in HUA mice.PMID:39924811 | DOI:10.1002/mnfr.202401017
Metabolic heterogeneity in tumor cells impacts immunology in lung squamous cell carcinoma
Oncoimmunology. 2025 Dec;14(1):2457797. doi: 10.1080/2162402X.2025.2457797. Epub 2025 Feb 9.ABSTRACTMetabolic processes are crucial in immune regulation, yet the impact of metabolic heterogeneity on immunological functions remains unclear. Integrating metabolomics into immunology allows the exploration of the interactions of multilayered features in the biological system and the molecular regulatory mechanism of these features. To elucidate such insight in lung squamous cell carcinoma (LUSC), we analyzed 106 LUSC tumor tissues. We performed high-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to obtain spatial metabolic profiles, and immunohistochemistry to detect tumor-infiltrating T lymphocytes (TILs). Unsupervised k-means clustering and Simpson's diversity index were employed to assess metabolic heterogeneity, identifying five distinct metabolic tumor subpopulations. Our findings revealed that TILs are specifically associated with metabolite distributions, not randomly distributed. Integrating a validation cohort, we found that heterogeneity-correlated metabolites interact with CD8+ TIL-associated genes, affecting survival. High metabolic heterogeneity was linked to worse survival and lower TIL levels. Pathway enrichment analyses highlighted distinct metabolic pathways in each subpopulation and their potential responses to chemotherapy. This study uncovers the significant impact of metabolic heterogeneity on immune functions in LUSC, providing a foundation for tailoring therapeutic strategies.PMID:39924768 | DOI:10.1080/2162402X.2025.2457797
Uncovering <em>de novo</em> polyamine biosynthesis in the gut microbiome and its alteration in inflammatory bowel disease
Gut Microbes. 2025 Dec;17(1):2464225. doi: 10.1080/19490976.2025.2464225. Epub 2025 Feb 9.ABSTRACTPolyamines are important gut microbial metabolites known to affect host physiology, yet the mechanisms behind their microbial production remain incompletely understood. In this study, we developed a stable isotope-resolved metabolomic (SIRM) approach to track polyamine biosynthesis in the gut microbiome. Viable microbial cells were extracted from fresh human and mouse feces and incubated anaerobically with [U-13C]-labeled inulin (tracer). Liquid chromatography-high resolution mass spectrometry analysis revealed distinct 13C enrichment profiles for spermidine (SPD) and putrescine (PUT), indicating that the arginine-agmatine-SPD pathway contributes to SPD biosynthesis in addition to the well-known spermidine synthase pathway (PUT aminopropylation). Species differences were observed in the 13C enrichments of polyamines and related metabolites between the human and mouse microbiome. By analyzing the fecal metabolomics and metatranscriptomic data from an inflammatory bowel disease (IBD) cohort, we found significantly higher polyamine levels in IBD patients compared to healthy controls. Further investigations using single-strain SIRM and in silico analyses identified Bacteroides spp. as key contributors to polyamine biosynthesis, harboring essential genes for this process and potentially driving the upregulation of polyamines in IBD. Taken together, this study expands our understanding of polyamine biosynthesis in the gut microbiome and will facilitate the development of precision therapies to target polyamine-associated diseases.PMID:39924644 | DOI:10.1080/19490976.2025.2464225
Combined transcriptional and metabolomic analysis of flavonoids in the regulation of female flower bud differentiation in Juglans sigillata Dode
BMC Plant Biol. 2025 Feb 10;25(1):168. doi: 10.1186/s12870-025-06121-9.ABSTRACTJuglans sigillata Dode is rich in flavonoids, but the low ratio of female to male flower buds limits the development of the J. sigillata industry. While the abundance of flavonoids in J. sigillata is known, whether flavonoids influence female flower bud differentiation has not been reported. In this study, we explored the regulatory mechanisms of gene expression and metabolite accumulation during female flower bud differentiation through integrated transcriptomic and metabolomic analyses. Our findings revealed that flavonoid biosynthesis is a key pathway influencing female flower bud differentiation, with metabolites primarily shifting towards the isoflavonoid, flavone, and flavonol branches. Structural genes such as chalcone synthase, dihydroflavonol 4-reductase, flavonol synthase, and flavonoid 3',5'-hydroxylase were identified as playing crucial regulatory roles. The expression of these genes promoted the accumulation of flavonoids, which in turn influenced female flower bud differentiation by modulating key regulatory genes including Suppressor of Overexpression of Constans1, Constans, Flowering Locus T, and APETALA1. Furthermore, transcription factors (TFs) highly expressed during the physiological differentiation of female flower buds, particularly M-type MADS, WRKY, and MYB, were positively correlated with flavonoid biosynthesis genes, indicating their significant role in the regulation of flavonoid production. These results offer valuable insights into the mechanisms of female flower bud differentiation in J. sigillata and highlight the regulatory role of flavonoids in plant bud differentiation.PMID:39924518 | DOI:10.1186/s12870-025-06121-9