PubMed

Arch Gerontol Geriatr. 2025 Feb 26;133:105803. doi: 10.1016/j.archger.2025.105803. Online ahead of print.ABSTRACTFrailty syndrome often coexists with multimorbidity, sharing several risk factors and outcomes. Therefore, considering multimorbidity when exploring frailty biomarkers may deepen our understanding of these conditions' pathophysiology. In this regard, most studies focused on inflammation, but markers of mitochondrial dysfunction, such as mitochondrial DNA damage, cell respiratory impairment, and oxidative stress, are less explored. The FRAMITO project aims to evaluate mitochondrial dysfunction in frailty, with and without multimorbidity. This cross-sectional study will enroll 75 individuals aged ≥65 years from inpatient and outpatient clinics at the Geriatrics Units of the University Hospital of Ferrara (Ferrara, Italy) and Fondazione IRCCS San Gerardo dei Tintori (Monza, Italy). Participants will be categorized into three groups: 25 without frailty and multimorbidity, 25 with frailty but not multimorbidity, and 25 with frailty and multimorbidity. Blood samples will be collected to isolate Peripheral Blood Mononuclear Cells. Frailty biomarkers will be identified using untargeted metabolomics and functional studies on mitochondrial dysfunctions in PBMCs and their subpopulations, evaluating mitochondrial DNA damage, mitochondrial and glycolytic cellular bioenergetics, and intracellular reactive oxygen species. This project will advance our understanding of mitochondrial dysfunctions in frailty, particularly when combined with multimorbidity, revealing potential synergistic effects. CLINICALTRIAL.GOV REGISTRATION NUMBER: NCT06433427.PMID:40043348 | DOI:10.1016/j.archger.2025.105803

J Proteome Res. 2025 Mar 5. doi: 10.1021/acs.jproteome.4c00881. Online ahead of print.ABSTRACTThe clustering of tandem mass spectra (MS/MS) is a crucial computational step to deduplicate repeated acquisitions in data-dependent experiments. This technique is essential in untargeted metabolomics, particularly with high-throughput mass spectrometers capable of generating hundreds of MS/MS spectra per second. Despite advancements in MS/MS clustering algorithms in proteomics, their performance in metabolomics has not been extensively evaluated due to the lack of database search tools with false discovery rate control for molecule identification. To bridge this gap, this study introduces the MS1-retention time (MS-RT) method to assess MS/MS clustering performance in metabolomics data sets. Here, we validate MS-RT by comparing MS-RT to established proteomics clustering evaluation approaches that utilize database search identifications. Additionally, we evaluate the performance of several MS/MS clustering tools on metabolomics data sets, highlighting their advantages and drawbacks. This MS-RT method and the MS/MS clustering tool benchmarking will provide valuable real world practical recommendations for tools and set the stage for future advancements in metabolomics MS/MS clustering.PMID:40042915 | DOI:10.1021/acs.jproteome.4c00881

Environ Health Perspect. 2025 Mar 5. doi: 10.1289/EHP15472. Online ahead of print.ABSTRACTBACKGROUND: Plastic cutting boards are commonly used in food preparation, increasing human exposure to microplastics (MPs). However, the health implications are still not well understood.OBJECTIVES: The objective of this study was to assess the impacts of long-term exposure to MPs released from cutting boards on intestinal inflammation and gut microbiota.METHODS: MPs were incorporated into mouse diets by cutting the food on polypropylene, polyethylene, and willow wooden cutting boards; diets were fed to mice over periods of 4 and 12 weeks. Serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), lipopolysaccharide (LPS, an endotoxin), and carcinoembryonic antigen (CEA), along with ileum and colon levels of IL-1β, TNF-α, malondialdehyde (MDA), superoxide dismutase (SOD), secretory immunoglobulin A (sIgA), and myosin light chain kinase (MLCK), were measured using mouse ELISA kits. The mRNA expression of mucin 2 and intestinal tight junction proteins in mouse ileum and colon tissues was quantified using real-time quantitative RT-PCR. Fecal microbiota, fecal metabolomics, and liver metabolomics were characterized.RESULTS: Polypropylene and polyethylene cutting boards released MPs, with concentrations reaching 1088 ± 95.0 and 1211 ± 322 µg g-1 in diets, respectively, and displaying mean particle sizes of 10.4 ± 0.96 vs 27.4 ± 1.45 µm. Mice fed diets prepared on polypropylene cutting boards for 12 weeks exhibited significantly higher serum levels of LPS, CRP, TNF-α, IL-10, and CEA, as well as higher levels of IL-β, TNF-α, MDA, SOD, and MLCK in the ileum and colon compared to mice fed diets prepared on willow wooden cutting boards. These mice also showed lower relative expression of Occludin and Zonula occludens-1 in the ileum and colon. In contrast, mice exposed to diets prepared on polyethylene cutting boards for 12 weeks did not show evident inflammation; however, there was a significant decrease in the relative abundance of Firmicutes and an increase in Desulfobacterota compared to those fed diets prepared on willow wooden cutting boards, while exposure to diets prepared on polyethylene cutting boards over 12 weeks also altered mouse fecal and liver metabolites compared to those fed diets prepared on willow wooden cutting boards.DISCUSSION: The findings suggest that MPs from polypropylene cutting boards impaired intestinal barrier function and induced inflammation, whereas those from polyethylene cutting boards affected the gut microbiota, gut metabolism, and liver metabolism in the mouse model. These findings offer crucial insights into the safe use of plastic cutting boards. https://doi.org/10.1289/EHP15472.PMID:40042913 | DOI:10.1289/EHP15472

Metabolomics. 2025 Mar 5;21(2):36. doi: 10.1007/s11306-025-02237-z.ABSTRACTINTRODUCTION: Garlic (Allium sativum L.) is renowned for its health-promoting properties, largely due to its sulfur-rich compounds. While copper is essential for plant growth and metabolism, excessive levels can disrupt cellular processes and lead to oxidative stress.OBJECTIVES: This study aims to investigate the impact of copper supplementation on the metabolic profile of garlic, with a particular focus on changes in sulfur metabolism.METHODS: Ito garlic cloves were harvested in 2020 on Red-Yellow Latosol soil. Copper chelate fertilizer was applied foliarly at 300 mL/ha, 30, 20, and 10 days before harvest. After harvesting, cloves were refrigerated and analyzed. Using LC-MS metabolomics, the metabolic profile of garlic was analyzed after copper supplementation to assess changes, specifically in sulfur-containing compounds.RESULTS: Copper supplementation led to a significant reduction in key sulfur-containing metabolites critical for the health-promoting properties of garlic, including allicin (FC = 0.0947), alliin (FC = 0.0147), and γ-glutamyl-S-allylcysteine (FC = 0.0076). Enrichment analysis identified alterations in pathways related to glutamine, glutamate, alanine, and aspartate metabolism. Additionally, precursors of glutathione (GSH) were depleted, likely as a result of GSH sparing efforts to counteract copper-induced oxidative stress. This redirection may increase susceptibility to ferroptosis, a form of cell death linked to oxidative damage.CONCLUSION: The metabolomic analysis of copper-supplemented Ito garlic cloves showed a significant reduction in sulfur compounds allicin, alliin, and γ-glutamyl-S-allylcysteine, important for organoleptic and medicinal properties. This decrease indicates a metabolic shift towards antioxidant defenses, with glutathione being redirected to defense pathways rather than secondary metabolites. Future studies should explore oxidative stress and ferroptosis markers, and lipidomics for a deeper understanding of garlic response to copper exposure.PMID:40042663 | DOI:10.1007/s11306-025-02237-z

Funct Integr Genomics. 2025 Mar 5;25(1):52. doi: 10.1007/s10142-025-01542-z.ABSTRACTAluminium toxicity and phosphorus deficiency are co-existing characteristics of low pH stress that significantly affect the grain yield of crops. The increasing acidity of Indian soils potentially limits the cultivable area for lentil (Lens culinaris), the third most widely consumed pulse. Breeding for tolerance requires an understanding of interdependent biological responses, but the molecular characterization of integrated tolerance remains elusive. Therefore, this study aimed to integrate high aluminium and low phosphorus stress responsive associations across the genomics, transcriptomics, proteomics, and metabolomics of multiple crop species. The overlapping molecular signatures were fine mapped to 23 candidates that serve multiple regulatory roles crucial for cellular homeostasis. Most of these genes have not been adequately discussed in the context of soil acidity tolerance. Thus, a multi-omics guided regulatory framework was developed to provide new insights into tolerance mechanisms. In silico genotyping of 29 lentil genotypes across 588 genes related to transomics loci yielded seven nonsynonymous and three synonymous variants likely associated with their differential response to stress. The results suggest comprehensive genotyping of multi-omics specific targets to identify potential candidates for marker-trait association studies. In conclusion, data-driven exploratory analysis of multi-omics variants highlights potential biomarkers as targets for genetically improving complex biological traits.PMID:40042647 | DOI:10.1007/s10142-025-01542-z

J Agric Food Chem. 2025 Mar 5. doi: 10.1021/acs.jafc.5c00375. Online ahead of print.ABSTRACTSoybeans are a valuable source of vegetable protein and edible oil. Fast neutron (FN) radiation was employed to produce large chromosomal deletions in soybean Glycine max (L.) Merrill. We conducted proteomic and metabolomic profiling of a high-protein soybean mutant (G15FN-12) developed through FN mutagenesis to identify the metabolic pathways that underlie the elevated protein content. A deletion of 137 genes located on chromosome-12 had occurred in G15FN-12. Tandem tag-based protein profiling of the mutant and wild type identified 6098 proteins, of which 175 showed increased abundance and 239 showed decreased abundance in the mutant seeds. Using liquid chromatography-mass spectrometry (LC-MS)-based metabolomic profiling, we identified 610 metabolites, of which 294 metabolites showed increased and 157 showed reduced content in mutant seeds as compared to wild type. Proteomic and metabolomic profiling revealed a decrease in ubiquitin-proteasome-associated proteins and an increase in heat shock proteins in the mutant seed. We hypothesize that decreased protein degradation, together with enhanced refolding of misfolded protein by molecular chaperones, contributes to elevated protein content in the mutant seed. The development of value-added seed traits such as increased protein using advanced metabolic engineering techniques can be achieved by further exploring the metabolic pathways identified in this investigation.PMID:40042580 | DOI:10.1021/acs.jafc.5c00375

Anesthesiology. 2025 Mar 5. doi: 10.1097/ALN.0000000000005435. Online ahead of print.ABSTRACTBACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain syndrome typically affecting a limb. It is characterized by severe spontaneous and evoked pain, along with vasomotor, autonomic, and motor signs and symptoms. Although dysregulation in several physiologic systems has been suggested in CRPS, including aberrant inflammatory and immune responses, vasomotor dysfunction, and nervous system changes, the pathophysiologic mechanisms underlying the syndrome remain elusive. Effective treatment options are also limited. Previous research has highlighted the role of the gut microbiome in chronic pain, prompting us to investigate the composition and function of the gut microbiome in CRPS.METHODS: The gut microbiomes of individuals with CRPS to age-, gender- and ethnicity-matched pain-free control participants were compared using 16S rRNA gene amplification. To minimize environmental confounders, participants were recruited from two geographically independent regions. To explore potential changes in gut-bacteria-derived metabolites targeted metabolomic analysis of feces and plasma was performed. Finally, machine learning algorithms were trained to identify the gut microbiome composition specific to CRPS patients and were tested on a validation cohort.RESULTS: In this study, differential abundance analysis revealed significant differences in several bacterial taxa when comparing 53 CRPS patients to 52 unrelated controls, including alterations in short-chain fatty acid (SCFA) metabolizing species. Targeted stool and plasma metabolite analysis confirmed differences in fecal and plasma SCFA levels between CRPS patients and controls. Notably, the microbiome composition alone allowed accurate classification of patients and controls in a geographically independent test cohort.CONCLUSIONS: These findings highlight unique compositional and functional changes in the gut microbiome of individuals with CRPS, thus contributing to the growing body of evidence supporting the role of the gut microbiome in chronic pain syndromes. Furthermore, they pave the way for further studies elucidating the pathophysiology of CRPS and exploring new diagnostic aids and treatment modalities.PMID:40042519 | DOI:10.1097/ALN.0000000000005435

Vet Ital. 2025 Mar 5;61(1). doi: 10.12834/VetIt.3578.29616.2.ABSTRACTDespite aggressive treatment, canine parvovirus (CPV) enteritis remains a major cause of morbidity and mortality in puppies. Identifying reliable biomarkers of CPV enteritis is important for determining severity, length of hospital stay, and predicting clinical outcomes. This the first study that aims to emphasize the relevance of the manuscript. Forty-three (43) CPV-infected dogs were diagnosed by a rapid antigen test kit and subsequent PCR, and 10 healthy dogs were enrolled. In this prospective study, metabolomics and cardiac troponin were measured by NMR and ELISA, respectively. The diseased dogs showed statistically significant lower levels of fructose, glucose, citrate, glycerate, glutamate, carnitine, glycine, formate, and higher levels of isoleucine, isovalerate, glycolate, and creatine compared with healthy dogs. The same analysis performed on lipid parameters showed statistically significant higher levels of cholesterol variants, fatty acyl variants, free cholesterol, glycerol backbone, and sphingomyelin and lower levels of phosphoglycerates and esterified cholesterol in the diseased groups. The changes in metabolomics could be attributed to energy deficit, fat mobilization, gluconeogenesis, tricarboxylic acid cycle deficiency, and multiple organ failure. Decreased citrate, and increased fatty acyl chain-CH2CO and sphingomyelin levels will serve as the most useful biomarkers in the prognosis of dogs suffering from CPV infection.PMID:40042380 | DOI:10.12834/VetIt.3578.29616.2

Biomed Chromatogr. 2025 Apr;39(4):e70029. doi: 10.1002/bmc.70029.ABSTRACTIdiopathic central precocious puberty (ICPP) is an endocrine disorder increasingly observed in children, commonly treated with gonadotropin-releasing hormone agonists (GnRHa). However, the serum lipid profiles in girls with ICPP and the potential regulatory effects of GnRHa in lipid metabolism remain unclear. This research analyzed lipidomic profiles of serum samples from girls younger than 10 years of age, including 37 patients with ICPP, 32 ICPP patients treated with GnRHa, and 30 age-matched healthy controls. Using UHPLC-Q-Exactive Orbitrap/MS, we identified a total of 898 differential lipids in both positive and negative modes, covering classes such as phosphatidylcholine (PC, including EtherPC), acylcarnitine (CAR), triglyceride (TG), N-acyl ethanolamines (NAEs), diacylglycerol (DG), sphingomyelin (SM), phosphatidylethanolamine (PE), ceramide (Cer), and fatty acids (FAs). In the ICPP cohort, 105 lipids exhibited significant differences compared with controls, with increased levels of CAR, SM, PC, PE, TG, and FA (p < 0.05), and notably decreased NAE levels (p < 0.05). Specifically, NAE 20:1 (AUC: 1.0), NAE 18:2 (AUC: 0.948), and NAE 20:0 (AUC: 0.895) were identified as potential diagnostic biomarkers for ICPP. Following GnRHa treatment, serum peak LH and FSH levels decreased, alongside reversible changes in 44 lipids, predominantly CAR, NAE, and TG. In conclusion, this study demonstrates that ICPP is associated with significant alterations in lipid metabolism. The lipidomic changes induced by GnRHa therapy suggest a potential link between ICPP treatment and lipid homeostasis, which warrants further investigation to refine therapeutic approaches for ICPP and potentially mitigate associated metabolic disorders.PMID:40042117 | DOI:10.1002/bmc.70029

Clin Endocrinol (Oxf). 2025 Mar 5. doi: 10.1111/cen.15226. Online ahead of print.ABSTRACTBACKGROUND: The incidence of precocious puberty (PP) has been on the rise in recent years. Based on different control mechanisms, childhood PP is divided into central precocious puberty (CPP) and peripheral precocious puberty (PPP). CPP accounts for 80% of all PP cases. Metabolomics is considered a link between genomics and phenotypes, providing a direct reflection of intricate biological traits. However, studies on serum metabolomic changes in CPP are very limited.METHODS: In this study, non-targeted metabolomics analysis of serum from healthy controls and CPP groups was performed. Serum samples were collected from a total of 55 individuals, including 30 girls diagnosed with CPP who had not yet received treatment and did not have any other comorbidities, and 25 healthy girls serving as controls who underwent physical examinations.RESULTS: A total of 1107 differential metabolites were identified, including 681 upregulated and 426 downregulated ones. The main pathway involved was citrate cycle (TCA cycle), primary bile acid biosynthesis, arginine biosynthesis, purine metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine biosynthesis, beta-alanine metabolism, taurine and hypotaurine metabolism, inositol phosphate metabolism, sphingolipid metabolism, pyruvate metabolism, propanoate metabolism, butanoate metabolism, C5-branched dibasic acid metabolism, sulphur metabolism, carbon metabolism and biosynthesis of amino acids.CONCLUSION: A total of 14 metabolites were identified through non-targeted metabolomics combined with four major metabolic network analyses. The above metabolites form a metabolic network that may serve as a novel marker and potential combined therapeutic target for the diagnosis of CPP.PMID:40042104 | DOI:10.1111/cen.15226

J Neurochem. 2025 Mar;169(3):e70030. doi: 10.1111/jnc.70030.ABSTRACTMicroglia, key immune cells in the brain, play a pivotal role in brain homeostasis and immune responses. Emerging evidence suggests their critical involvement in Alzheimer's disease (AD) pathogenesis and propagation. The propagation of AD pathology is related to the extracellular matrix of microglia, including extracellular vesicles (EV). Recently, microglia-derived EVs are implicated in inflammatory processes and neuronal death. This study aimed to extensively profile and propose the metabolic role of microglial EVs in AD. Accordingly, we determined the significant alterations of the EV metabolome associated with the metabolites in primary microglial cells. Aβ exposure induced significant metabolic alteration of 39, 18, and 28 metabolites in microglial cells, cultured media, and EVs, respectively. Aβ exposure triggered common alteration of key metabolic pathways between microglial cells and EVs, including purine, amino acid, and fatty acid metabolisms. While most of the common metabolites showed the same directional changes among the microglial system, N-acetyl aspartic acid displayed the opposite directional change in EVs. N-acetyl aspartic acid decreased 2.3-fold and twofold in microglial cells and media, respectively, but increased 3.5-fold in EVs under Aβ exposure. Moreover, mediation analysis proposed key EV metabolites that were directly affected by the metabolic dysregulation of Aβ-exposed microglial cells. The up-regulation of cysteic acid in EVs was mediated by up-regulated IMP in microglial cells. The down-regulation of 1-16:0-lysoPE in EVs was mediated by stearoyl-L-carnitine in microglial cells. Our study sheds new light on the role of microglia and EVs in neurodegenerative diseases, offering promising avenues for future therapeutic interventions.PMID:40042046 | DOI:10.1111/jnc.70030

Adv Sci (Weinh). 2025 Mar 5:e2415041. doi: 10.1002/advs.202415041. Online ahead of print.ABSTRACTCertain medications, including cisplatin and neomycin, often cause both hearing loss and renal dysfunction. This study aims to uncover the common mechanisms behind drug-induced ototoxicity and nephrotoxicity to aid early diagnosis and treatment. Metabolomic analyses reveal simultaneous disruptions in endogenous metabolic networks in the kidney, inner ear, and serum after administrating cisplatin or neomycin. Notably, a marked elevation in uric acid (UA), a recognized indicator of renal tubular injury, is identified. Supplementing UA and inhibiting its renal excretion worsen hearing loss and hair cell damage. Single-cell nucleus sequencing and immunohistochemistry reveal major changes in xanthine oxidase and ABCG2, crucial for UA metabolism, primarily in cochlear stria vascularis cells rather than hair cells. Cisplatin triggers a significant release of UA from stria vascularis cells, reaching concentrations sufficient to induce autophagy-dependent ferroptosis in hair cells. In a coculture system, targeted interventions against these two proteins in stria vascularis cells, through either pharmacological inhibition or genetic manipulation, markedly decrease the elevated UA release and the subsequent ferroptosis of hair cells. These findings suggest a metabolic connection between the inner ear and the kidney, highlighting the therapeutic potential of modulating UA to mitigate drug-induced nephrotoxicity and ototoxicity.PMID:40041973 | DOI:10.1002/advs.202415041

J Exp Zool A Ecol Integr Physiol. 2025 Mar 5. doi: 10.1002/jez.2912. Online ahead of print.ABSTRACTIn the integrated rice-crayfish aquaculture systems, crayfish Procambarus clarkii need to spend a long winter in the ring ditch, which is vulnerable to low temperature stress, especially in the northern part of China, where cold waves and other low-temperature climates are frequent. To study the metabolic response of P. clarkii to low temperature stress experimentally, the temperature was lowered from the control (23°C) to the low temperature group (9°C, 5°C, and 1°C) by slow and uniform cooling, and molecular and physiological samples were collected for measurement. The results showed that low temperature stress damaged the gill membrane and the epithelial layer of gill tissues, with an increase in vacuoles area and a reduced and irregular distribution of hemocytes. As the temperature decreased, the oxygen consumption rate, ammonia excretion rate and maximum metabolic rate of P. clarkii decreased gradually, the oxygen-nitrogen ratio decreased but still remained at a high level, and the metabolic energy supply substances were always mainly lipids and carbohydrates. The pyruvate kinase activity tended to increase with decreasing temperature under low temperature stress, while hexokinase, succinate dehydrogenase and lactate dehydrogenase activities decreased gradually. The 183 differential metabolites were screened in the low temperature group compared with the control mostly enriched in amino acid metabolism and citrate cycle metabolic pathways. In conclusion, under low temperature stress, the gill was damaged, respiratory metabolism decreased, and glycolysis was enhanced. Since the citrate cycle metabolism was suppressed, P. clarkii needed to resist low temperature stress by increasing the amino acid metabolism to provide more energy to maintain cellular activity. The results unraveled metabolic response mechanisms of metabolic response mechanism of P. clarkii to low temperature stress, and provided theoretical references for the selection and breeding of low-temperature-tolerant strains of P. clarkii.PMID:40041957 | DOI:10.1002/jez.2912

Acta Pharm Sin B. 2025 Jan;15(1):239-255. doi: 10.1016/j.apsb.2024.10.003. Epub 2024 Oct 15.ABSTRACTIncreasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.PMID:40041923 | PMC:PMC11873608 | DOI:10.1016/j.apsb.2024.10.003

Acta Pharm Sin B. 2025 Jan;15(1):205-223. doi: 10.1016/j.apsb.2024.11.009. Epub 2024 Nov 22.ABSTRACTDisruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.PMID:40041900 | PMC:PMC11873645 | DOI:10.1016/j.apsb.2024.11.009

Front Microbiol. 2025 Feb 18;16:1529596. doi: 10.3389/fmicb.2025.1529596. eCollection 2025.ABSTRACTThis study aimed to investigate the effects of rumen-protected guanidinoacetic acid (RP-GAA) on growth performance, gut microbiota, and serum metabolism in beef cattle under chronic heat stress. A randomized block design was employed to allocate 14 F1 Simmental crossbred cattle (Simmental ♂ × Bos indicus ♀) with an average body weight of 312.5 ± 55.0 kg into two groups (n = 7): a control group was fed a basal diet without RP-GAA and a treatment group was fed the same basal diet supplemented with 10.0 g/day of RP-GAA. During feeding experiments, at 2 p.m., the average temperature increased to 31.5°C, with a relative humidity of 69.5% and a THI of 83.2. All animals are under chronic heat stress. The results indicated that RP-GAA supplementation significantly increased dry matter intake and feed conversion ratio in beef cattle under chronic heat stress (p < 0.05). RP-GAA supplementation tended to reduce respiratory rate or rectal temperature (p < 0.1). Compared to the control group, the treatment group exhibited significantly higher glucose, blood urea nitrogen, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels (p < 0.05). 16S rRNA gene sequencing revealed that RP-GAA supplementation significantly altered the ruminal microbiota composition, increasing the abundance of Firmicutes and Bacteroidota (p < 0.05), while reducing Proteobacteria (p < 0.01). Principal coordinate analysis (PCoA) and Adonis test (R 2 = 0.190, p = 0.003) jointly revealed a distinct difference in fecal microbiota structures between the two groups. Metabolomic analysis identified significant changes in pathways related to creatine synthesis, energy metabolism, and nitrogen utilization, supported by the orthogonal partial least squares discriminant analysis model (R 2 Y = 0.983, Q 2 = 0.836, p < 0.05). These findings suggest that RP-GAAenhances energy homeostasis, supports gut health, and mitigates the adverse effects of heat stress, providing a promising strategy to improve production efficiency and animal welfare in heat-stressed cattle.PMID:40041874 | PMC:PMC11877906 | DOI:10.3389/fmicb.2025.1529596

Front Microbiol. 2025 Feb 18;16:1530319. doi: 10.3389/fmicb.2025.1530319. eCollection 2025.ABSTRACTINTRODUCTION: Pediococcus acidilactici CNCM I-4622 (PA) is a homofermentative Gram-positive coccus that produces lactic acid as a major metabolic by-product. However, the potential of PA to improve intestinal function and, as a result, improve production performance and quality in aged laying hens remains unclear. This study aimed to investigate the effects of PA on egg production, egg quality, intestinal health, and cecal microbiota in aged laying hens.METHODS: A total of 180 Lohmann pink laying hens, aged 80 weeks, were randomly assigned to five groups and fed either a basal diet (PA0) or basal diets supplemented with PA at concentrations of 50, 100, 150, and 200 mg/kg (PA50, PA100, PA150, and PA200).RESULTS: Compared to the PA0 group, PA did not have a significant effect on the production performance of laying hens (p > 0.05). However, the content of diamine oxidase and the expression level of IL-8 mRNA in the PA50, P100, P150, and P200 groups were significantly reduced (p < 0.05). Additionally, the ileal villus height was significantly increased (p < 0.05). The cecal chowder pH and ileal crypt depth were also significantly lower (p < 0.05), while lipase activity in the ileal mucosa of the PA50 group was significantly increased compared to the PA0 group (p < 0.05). Furthermore, the expression of INF-γ and TNF-α mRNA in the jejunal mucosa was significantly down-regulated (p < 0.05), whereas the expression of Claudin mRNA was significantly up-regulated (p < 0.05). Notably, the relative abundance of Bacteroidota, Fusobacteriota, and Fusobacterium in the PA50 group was significantly higher than that in the PA0 group (p < 0.05).DISCUSSION: Additionally, cecal metabolomic analysis indicated that following the addition of PA, the pathways enriched with differential metabolites were primarily related to arginine and proline metabolism. Therefore, PA has the potential to improve intestinal morphology and flora, mitigate intestinal inflammatory factors, and strengthen intestinal barrier function. These benefits are attributed to the modulation of arginine and proline metabolic pathways, with optimal effects observed at an addition of 50 mg/kg.PMID:40041866 | PMC:PMC11877211 | DOI:10.3389/fmicb.2025.1530319

Res Pract Thromb Haemost. 2025 Jan 9;9(1):102677. doi: 10.1016/j.rpth.2025.102677. eCollection 2025 Jan.ABSTRACTBACKGROUND: VITT has emerged as a rare but serious adverse event linked primarily to adenoviral vector COVID-19 vaccinations, such as ChAdOx1-S (Oxford/AstraZeneca) vaccination. The syndrome is characterized by thrombosis with thrombocytopenia, elevated D-dimer, and pathologic platelet factor 4 antibodies within 42 days of vaccination.OBJECTIVES: Despite dysregulated lipid metabolism underpinning many thrombotic conditions, the role of lipid alterations in VITT remains unexplored. Here, we examined the plasma lipidome of patients with VITT and compared it with those following ChAdOx1-S vaccination and with unprovoked venous thromboembolism (VTE) to understand the role of lipids in VITT pathophysiology.METHODS: This was a multicenter, prospective cohort study evaluating plasma lipidomics in newly diagnosed VITT samples, which were compared with both healthy controls following ChAdOx1-S vaccination and with unprovoked VTE.RESULTS: Comparison with ChAdOx1-S controls reveals a distinct lipid signature in VITT, characterized by elevations in phosphatidylserine and ceramide species, alongside reductions in several plasmalogens and acylcarnitine species. Notably, similarities between VITT lipid profiles and insulin resistance phenotypes suggest potential metabolic susceptibility. While few significant associations were found between VITT and VTE, an inverse correlation with several acylcarnitine species was demonstrated. Given the known anticoagulant role of acylcarnitine species, these findings suggest a plausible mechanistic pathway elevating the thrombotic potential of VITT above that of standard VTE.CONCLUSION: These findings underscore the important role of lipid metabolism in VITT pathophysiology and highlight the complex interplay between lipids, coagulation, and pathologic thrombosis.PMID:40041449 | PMC:PMC11879676 | DOI:10.1016/j.rpth.2025.102677

Biochem Biophys Rep. 2025 Feb 18;41:101943. doi: 10.1016/j.bbrep.2025.101943. eCollection 2025 Mar.ABSTRACTOBJECTIVE: To investigate the associations between metabolic changes and functions, including energy metabolism, immune response, and redox balance, under short-term hypobaric hypoxia exposure. Non-targeted metabolomics and bioinformatics analysis were applied to explore the adaptive mechanisms of organisms in hypobaric hypoxia.METHODS: Healthy adult male Sprague-Dawley rats were placed in environments simulating altitudes of 6500 m (HC group) and 1588 m (Control group). After 14 days, arterial serum samples were analyzed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Significant metabolites (P < 0.05, VIP >1) were identified, and KEGG enrichment analysis was conducted. Differential metabolites were globally analyzed with MetaboAnalyst 5.0.RESULTS: A total of 117 significantly altered metabolites were identified. In the HC group, 84 metabolites significantly increased, while 33 metabolites significantly decreased compared to the Control group. KEGG enrichment analysis revealed significant metabolic pathways, including the PPAR signaling pathway, bile secretion, arginine biosynthesis, alcoholism, and cholesterol metabolism (P < 0.05). Global analysis indicated that these differential metabolites were involved in various pathways, such as energy metabolism, amino acid metabolism, nucleotide metabolism, lipid metabolism, vitamin and cofactor metabolism, steroid metabolism, neurotransmitter metabolism, and heme metabolism, all of which play crucial roles in multiple biological processes.CONCLUSION: Short-term hypobaric hypoxia exposure significantly altered the metabolite profiles in the arterial serum samples of rats, revealing adaptive metabolic reprogramming in energy metabolism, redox balance, immune function, endocrine regulation, and neurological systems.PMID:40041253 | PMC:PMC11876769 | DOI:10.1016/j.bbrep.2025.101943

Front Cell Infect Microbiol. 2025 Feb 18;15:1511900. doi: 10.3389/fcimb.2025.1511900. eCollection 2025.ABSTRACTINTRODUCTION: Body mass index (BMI) is considered an important factor in tumor prognosis, but its role in gastric cancer (GC) remains controversial. There is a lack of studies exploring the effect of BMI on gastric cancer from the perspective of intratumoral microbiota. This study aimed to compare and analyze the differences in and functions of intratumoral microbiota among GC patients with varying BMIs, aiming to ascertain whether specific microbial features are associated with prognosis in low-BMI (LBMI) gastric cancer patients.METHODS: A retrospective analysis of the clinicopathological features and prognosis of 5567 patients with different BMIs was performed between January 2010 and December 2019. Tumor tissues from 189 GC patients were collected for 16S rRNA sequencing, 64 samples were selected for transcriptome sequencing, and 57 samples were selected for untargeted metabolomic analysis.RESULTS: Clinical cohort analysis revealed that GC patients with a low BMI presented poorer clinical and pathological characteristics than those with a non-low-BMI (NLBMI). LBMI was identified as a significant independent risk factor for adverse prognosis, potentially exerting immunosuppressive effects on postoperative adjuvant chemotherapy. 16S rRNA sequencing revealed no significant differences in the alpha and beta diversity of the intratumoral microbiota between the two groups of GC patients. However, LEfSe analysis revealed 32 differential intratumoral microbiota between the LBMI and NLBMI groups. Notably, the genus Abiotrophia was significantly enriched in the LBMI group. Further in-depth analysis indicated that the genus Abiotrophia was inversely associated with eosinophils, P2RY12, and SCN4B genes, and positively linked with LGR6 in LBMI gastric cancer patients. Metabolomic assessments revealed that LBMI was positively associated with purine metabolites, specifically guanine and inosine diphosphate (IDP).DISCUSSION: In conclusion, LBMI is an independent risk factor for poor prognosis in gastric cancer patients and may have an inhibitory effect on postoperative adjuvant chemotherapy. Intratumor flora of gastric cancer patients with different BMI levels differed, with different immune cell infiltration and metabolic characteristics. The genus Abiotrophia may promote gastric cancer development and progression by regulating eosinophils and the purine metabolism pathway, which provides a new idea for the precise treatment of gastric cancer.PMID:40041144 | PMC:PMC11876552 | DOI:10.3389/fcimb.2025.1511900