PubMed

Gut Microbes. 2024 Jan-Dec;16(1):2431648. doi: 10.1080/19490976.2024.2431648. Epub 2024 Dec 16.ABSTRACTMultiple emerging lines of evidence indicate that the microbiome contributes to aging and cognitive health. However, the roles of distinct microbial components, such as viruses (virome) and their interactions with bacteria (bacteriome), as well as their metabolic pathways (metabolome) in relation to aging and cognitive function, remain poorly understood. Here, we present proof-of-concept results from a pilot study using datasets (n = 176) from the Microbiome in Aging Gut and Brain (MiaGB) consortium, demonstrating that the human virome signature significantly differs across the aging continuum (60s vs. 70s vs. 80+ years of age) in older adults. We observed that the predominant virome signature was enriched with bacteriophages, which change considerably with aging continuum. Analyses of interactions between phages and the host bacteriome suggest that lytic or temperate relationships change distinctly across the aging continuum, as well as cognitive impairment. Interestingly, the phage-bacteriome-metabolome interactions develop unique patterns that are distinctly linked to aging and cognitive dysfunction in older adults. The phage-bacteriome interactions affect bacterial metabolic pathways, potentially impacting older adults' health, including the risk of cognitive decline and dementia. Further comprehension of these studies could provide opportunities to target the microbiome by developing phage therapies to improve aging and brain health in older adults.PMID:39676708 | DOI:10.1080/19490976.2024.2431648

Am J Med Genet A. 2024 Dec 16:e63971. doi: 10.1002/ajmg.a.63971. Online ahead of print.ABSTRACTMonozygotic (MZ) and dizygotic (DZ) twins are studied to understand genetic and environmental influences on complex traits, however the mechanisms behind twinning are not completely understood. (Epi)genomic studies identified SNPs associated with DZ twinning and DNA methylation sites with MZ twinning. To find molecular biomarkers of twinning, we compared transcriptomics and metabolomics data from MZ and DZ twins. We analyzed 42,663 RNA transcripts in 1453 MZ twins and 1294 DZ twins from the Netherlands Twin Register (NTR), followed by sex-stratified analyses. The top 5% transcripts with lowest p-values were analyzed for replication in 217 MZ and 158 DZ twins from the older Finnish Twin cohort (FTC). In the NTR, one transcript (PURG) was significantly differentially expressed between MZ and DZ twins; but this did not replicate in FTC. Pathway analyses highlighted the WNT-pathway, previously associated with MZ twinning, and the TGF-B and SMAD pathway, previously associated with DZ twinning. Meta-analysis of 169 serum metabolites in 2797 MZ and 2040 DZ twins from the NTR, FTC and FinnTwin12, showed no metabolomic differences. Overall, we did not find replicable transcript-level expression differences in blood between MZ and DZ twins, but highlighted the TGF-B/SMAD pathway as a potential transcriptional biomarker for DZ twinning.PMID:39676692 | DOI:10.1002/ajmg.a.63971

J Appl Toxicol. 2024 Dec 15. doi: 10.1002/jat.4743. Online ahead of print.ABSTRACTThe clinical application of cantharidin (CTD) is seriously limited due to its nephrotoxicity. Therefore, this study aims to investigate sensitive biomarkers for the evaluation and prediction of nephrotoxicity induced by CTD in rat. A total of 80 rats were randomly divided into four groups: control group and three doses of CTD groups. After 0, 1, 5, 15, and 28 days of intragastric administration, rat serum and urine were collected for biochemical indexes, then serum was used for metabolomic analyses, and rat kidney was collected for pathological and ultrastructural observation. The levels of serum crea (Scr), blood urea nitrogen (BUN), urea, urine crea (Ucrea), and urinary microalbumin (UmALB) were significantly increased after administration of different doses of CTD (p < 0.05). Additionally, histopathology and cell ultrastructure observation of kidney showed significant cell inflammatory infiltration and glomerular edema. Seven metabolic biomarkers including 6-hydroxymelatonin were significantly disturbed by CTD. The CatBoost Classifier prediction model was used to establish the CTD nephrotoxicity prediction model, and the prediction accuracy and precision were 0.645 and 0.640, respectively. Moreover, 6-hydroxymelatonin was found to be most useful biomarkers for evaluating the CTD nephrotoxicity. Finally, the seven metabolic biomarkers were found mainly involved in pyruvate metabolism, pantothenate and CoA biosynthesis.PMID:39676217 | DOI:10.1002/jat.4743

Metabolomics. 2024 Dec 15;21(1):9. doi: 10.1007/s11306-024-02199-8.ABSTRACTINTRODUCTION: Outside of case-control settings, ethnicity specific changes in the human metabolome are understudied especially in community dwelling, ageing men. Characterising serum for age and ethnicity specific features can enable tailored therapeutics research and improve our understanding of the interplay between age, ethnicity, and metabolism in global populations.OBJECTIVE: A metabolomics approach was adopted to profile serum metabolomes in middle-aged and elderly men of different ethnicities from the Northwest of England, UK.METHODS: Serum samples from 572 men of White European (WE), South Asian (SA), and African-Caribbean (AC) ethnicities, ranging between 40 and 86 years were analysed. A combination of liquid chromatography (LC) and gas chromatography (GC) coupled to high-resolution mass spectrometry (MS) was used to generate the metabolomic profiles. Partial Least Squares Discriminant Analysis (PLS-DA) based classification models were built and validated using resampling via bootstrap analysis and permutation testing. Features were putatively annotated using public Human Metabolome Database (HMDB) and Golm Metabolite Database (GMD). Variable Importance in Projection (VIP) scores were used to determine features of interest, after which pathway enrichment analysis was performed.RESULTS: Using profiles from our analysis we classify subjects by their ethnicity with an average correct classification rate (CCR) of 90.53% (LC-MS data) and 85.58% (GC-MS data). Similar classification by age (< 60 vs. ≥ 60 years) returned CCRs of 90.20% (LC-MS) and 71.13% (GC-MS). VIP scores driven feature selection revealed important compounds from putatively annotated lipids (subclasses including fatty acids and carboxylic acids, glycerophospholipids, steroids), organic acids, amino acid derivatives as key contributors to the classifications. Pathway enrichment analysis using these features revealed statistically significant perturbations in energy metabolism (TCA cycle), N-Glycan and unsaturated fatty acid biosynthesis linked pathways amongst others.CONCLUSION: We report metabolic differences measured in serum that can be attributed to ethnicity and age in healthy population. These results strongly emphasise the need to consider confounding effects of inherent metabolic variations driven by ethnicity of participants in population-based metabolic profiling studies. Interpretation of energy metabolism, N-Glycan and fatty acid biosynthesis should be carefully decoupled from the underlying differences in ethnicity of participants.PMID:39676138 | DOI:10.1007/s11306-024-02199-8

Metabolomics. 2024 Dec 15;21(1):7. doi: 10.1007/s11306-024-02202-2.ABSTRACTBACKGROUND: Soccer is the most recognized sports worldwide. It is a fertile ground for the use of metabolomics analyses, considering the multifactorial nature of soccer's physical demands on the body. Although scientific studies have tried using it to better understand the impacts of soccer into different contexts of the sport, no systematic review is available on metabolomics analyses in soccer athletes subjected to physical exertion interventions.AIM OF REVIEW: Retrieve scientific articles that conducted metabolomics analyses on soccer athletes subjected to physical exertion interventions.KEY SCIENTIFIC CONCEPTS OF REVIEW: Initially, 271 studies were screened, and 48 were retrieved for abstract analysis. Of these, 26 met the eligibility criteria, but 5 failed to meet inclusion criteria. The 21 studies included in this systematic review demonstrate that responses from physical training or acute exercise sessions, followed by the effects of soccer matches, have been the primary focus of researchers to date, highlighting alterations on metabolites from the energy metabolism, immunological pathway, purines, tryptophan/phenylalanine metabolism, as well as oxidative species and antioxidant capacity. Other studies suggest, albeit preliminarily, that organic metabolites have the potential to distinguish soccer players' performance and physical fitness, as well as provide valuable insights into diet, physical condition, training load, and recovery throughout the season. Despite metabolomics great potential to understand physiological alterations provoked by soccer as shown by the included studies, future studies should consider female athletes, explore the cause-and-effect relationship between metabolites and soccer performance more deeply, and examine the effects of different training periodizations on these markers.PMID:39676125 | DOI:10.1007/s11306-024-02202-2

Metabolomics. 2024 Dec 15;21(1):6. doi: 10.1007/s11306-024-02207-x.ABSTRACTBACKGROUND: Due to the high prevalence of myopia, there is a growing need for the identification of myopia intervention mechanisms and targets. Metabolomics has been gradually used to investigate changes in myopia tissue metabolites over the last few years, but the potential physiological and pathological roles of amino acids and their downstream metabolites discovered by metabolomics in myopia are not fully understood.AIM OF REVIEW: Aim to explore the possible relationship between amino acid metabolism and the occurrence and development of myopia, we collected a total of 21 experimental studies related to myopia metabolomics. Perform pathway analysis using MetaboAnalyst online software. We have identified over 20 amino acids that may be associated with the development of myopia. Among them, 19 types of amino acids are common amino acids. We discussed their possible mechanisms affecting myopia and proposed future prospects for treating myopia.KEY SCIENTIFIC CONCEPTS OF REVIEW: Our analysis results show that metabolomics research on myopia involves many important amino acids. We have collected literature and found that research on amino acid metabolism in myopia mainly focuses on downstream small molecule substances. Amino acids and their downstream metabolites affect the development of myopia by participating in important biochemical processes such as oxidative stress, glucose metabolism, and lipid metabolism. Enzymes, receptors, and cytokines that regulate amino acid metabolism may become potential targets for myopia treatment.PMID:39676079 | DOI:10.1007/s11306-024-02207-x

Metabolomics. 2024 Dec 15;21(1):8. doi: 10.1007/s11306-024-02206-y.ABSTRACTINTRODUCTION: Rapid detection and identification of pathogens and antimicrobial susceptibility is essential for guiding appropriate antimicrobial therapy and reducing morbidity and mortality associated with sepsis.OBJECTIVES: The metabolic response of clinical isolates of Klebsiella oxytoca exposed to different concentrations of ciprofloxacin (the second generation of quinolones antibiotics) were studied in order to investigate underlying mechanisms associated with antimicrobial resistance (AMR).METHODS: Metabolomics investigations were performed using Fourier-transform infrared (FT-IR) spectroscopy as a metabolic fingerprinting approach combined with gas chromatography-mass spectrometry (GC-MS) for metabolic profiling.RESULTS: Our findings demonstrated that metabolic fingerprints provided by FT-IR analysis allowed for the differentiation of susceptible and resistant isolates. GC-MS analysis validated these findings, while also providing a deeper understanding of the metabolic alterations caused by exposure to ciprofloxacin. GC-MS metabolic profiling detected 176 metabolic features in the cellular extracts cultivated on BHI broth, and of these, 137 could be identified to Metabolomics Standards Initiative Level 2. Data analysis showed that 40 metabolites (30 Level 2 and 10 unknown) were differentiated between susceptible and resistant isolates. The identified metabolites belonging to central carbon metabolism; arginine and proline metabolism; alanine, aspartate and glutamate metabolism; and pyruvate metabolism. Univariate receiver operating characteristic (ROC) curve analyses revealed that six of these metabolites (glycerol-3-phosphate, O-phosphoethanolamine, asparagine dehydrate, maleimide, tyrosine, and alanine) have a crucial role in distinguishing susceptible from resistant isolates (AUC > 0.84) and contributing to antimicrobial resistance in K. oxtytoca.CONCLUSION: Our study provides invaluable new insights into the mechanisms underlying development of antimicrobial resistance in K. oxytoca suggests potential therapeutic targets for prevention and identification of AMR in K. oxytoca infections.PMID:39676074 | DOI:10.1007/s11306-024-02206-y

J Biol Chem. 2024 Dec 13:108091. doi: 10.1016/j.jbc.2024.108091. Online ahead of print.ABSTRACTNeutrophils are a part of the innate immune system and produce reactive oxygen species (ROS) to extinguish pathogens. The major source of ROS in neutrophils is NADPH oxidase, which is fueled by NADPH generated via the pentose phosphate pathway; however, it is unclear how other accessory glucose metabolism pathways and mitochondrial activity influence the respiratory burst. We examined the temporal dynamics of the respiratory burst and delineated how metabolism changes over time after neutrophil activation. Bone marrow-derived neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA), and the respiratory burst was measured via extracellular flux analysis. Metabolomics experiments utilizing 13C6-glucose highlighted the activation of glycolysis as well as ancillary pathways of glucose metabolism in activated neutrophils. PMA stimulation acutely increased 13C enrichment into glycerol 3-phosphate (G3P) and citrate, whereas increases in 13C enrichment in the glycogen intermediate, UDP-hexose, and end products of the hexosamine and serine biosynthetic pathways occurred only during the late phase of the oxidative burst. Targeted inhibition of the G3P shuttle, glycogenolysis, serine biosynthesis, and mitochondrial respiration demonstrated that the G3P shuttle contributes to the general magnitude of ROS production; that glycogen contributes solely to the early respiratory burst; and that the serine biosynthetic pathway activity and Complex III-driven mitochondrial activity influence respiratory burst duration. Collectively, these results show that the neutrophil oxidative burst is highly dynamic, with coordinated changes in metabolism that control the initiation, magnitude, and duration of ROS production.PMID:39675714 | DOI:10.1016/j.jbc.2024.108091

Pharmacol Res. 2024 Dec 13:107550. doi: 10.1016/j.phrs.2024.107550. Online ahead of print.ABSTRACTObesity-related glomerulopathy (ORG) represents an escalating public health with no effective treatments currently available. Abnormal lipid metabolism and lipid droplet deposition in the kidneys are key contributors to ORG. Cyanidin-3-glucoside (C3G) has shown potential in regulating lipid metabolism and may offer reno-protective effects; however, its therapeutic efficacy and underlying mechanisms in ORG remain unclear. An ORG mouse model was established, followed by an 8-week C3G intervention. The mice were divided into three groups: normal control (CT) group, ORG group, and C3G treatment group. Fecal 16S rRNA sequencing, metabolomics of feces-serum-kidney, and kidney single-cell RNA sequencing (scRNA-seq) were performed to investigate the effects and mechanisms of C3G. Compared to CT mice, ORG mice exhibited elevated serum CHO, TG, Cys-C, UACR, urinary Kim-1, and NAG levels, along with glomerular hypertrophy and tubular injury. These biochemical and pathological indicators improved following C3G treatment. Fecal 16S analysis revealed reduced gut microbiota diversity in ORG mice compared to CT mice, while C3G intervention increased gut microbiota diversity. Metabolic profiling of feces, serum, and kidney indicated reprogramming of glycerophospholipid metabolism in ORG mice, ameliorated by C3G treatment. Further analysis demonstrated that abnormal glycerophospholipid metabolites correlated with blood lipids, urinary protein, urinary tubular injury markers, and gut microbiota, specifically Lachnospiraceae and Blautia. Additionally, scRNA-seq analysis identified activation of the PPARγ/CD36 pathway in proximal tubule cells (PTCs) of ORG mice. C3G improved abnormal glycerophospholipid metabolism and alleviated injury in PTCs by inhibiting the PPARγ/CD36 pathway. C3G reduces lipid droplet accumulation in the PTCs of ORG mice by modulating the gut microbiota and inhibiting the PPARγ/CD36 pathway. These findings offer new insights and therapeutic targets for ORG.PMID:39675540 | DOI:10.1016/j.phrs.2024.107550

Free Radic Biol Med. 2024 Dec 13:S0891-5849(24)01138-9. doi: 10.1016/j.freeradbiomed.2024.12.029. Online ahead of print.ABSTRACTBACKGROUND: Neuronal protection is a well-established method of acute ischemic stroke (AIS) treatment. The pharmacodynamic effect of Piceatannol-3'-O-β-D-glucopyranoside (Chinese name: Quzhazhigan, QZZG) on AIS has been reported, but the molecular mechanism of this effect remains unknown.PURPOSE: The purpose of this study is to elucidate the pharmacodynamic effects and mechanisms of QZZG in the treatment of AIS.METHODS: A combined network pharmacology and metabolomics approach was used to predict the key targets and pathways of QZZG in the treatment of AIS and to elucidate the mechanism of QZZG through experimental validation.RESULTS: In this study, QZZG improved histopathologic features and reduced infarct volume and neurologic deficit scores. Integrated network pharmacology and metabolomics revealed that QZZG may protect neurons by regulating glutamate and its receptors, and that glutamate is closely related to NMDAR1, NRF2, and Caspase-3. Pathway analysis results suggested that NMDAR-mediated Ca2+ inward flow is one of the critical pathways. In terms of neuroexcitotoxicity QZZG inhibited glutamate content, reduced Ca2+ inward flow, protected mitochondrial function, and reduced ROS, as well as being able to effectively inhibit the expression of NMDAR1, Caspase-3, Bax, and promote the expression of Bcl-2, NMDAR2A. In terms of ferroptosis QZZG promoted NRF2, HO-1, GPX4 and nuclear-NRF2, inhibited the expression of BACH1 and ACSL4, and suppressed Fe2+ accumulation and lipid peroxidation. Silencing of BACH1 resulted in elevated expression of NRF2 and decreased expression of ACSL4, which inhibited the sensitivity of neurons to ferroptosis. QZZG was able to further increase NRF2 expression under conditions of silencing BACH1. QZZG induced NRF2 and inhibited BACH1, ACSL4 was inhibited by ML385, and inhibition of NRF2 induced the expression of BACH1 and ACSL4, QZZG protects neurons in an NRF2-dependent manner.CONCLUSION: In summary, QZZG inhibited neuroexcitotoxicity and ferroptosis by regulating the NMDAR/NRF2/BACH1/ACSL4 pathway. The study provided a relatively novel perspective on the mechanism of traditional Chinese medicine (TCM) treatment of the disease.PMID:39675532 | DOI:10.1016/j.freeradbiomed.2024.12.029

J Lipid Res. 2024 Dec 13:100730. doi: 10.1016/j.jlr.2024.100730. Online ahead of print.ABSTRACTLong-chain acyl-CoA synthetase 1 (ACSL1) catalyzes the conversion of long-chain fatty acids to acyl-CoAs. ACSL1 is required for β-oxidation in tissues that rely on fatty acids as fuel, but no consensus exists on why ACSL1 is induced by inflammatory mediators in immune cells. We used a comprehensive and unbiased approach to investigate the role of ACSL1 induction by interferon type I (IFN-I) in myeloid cells in vitro and in a mouse model of IFN-I overproduction. Our results show that IFN-I induces ACSL1 in macrophages via its interferon-α/β receptor, and consequently that expression of ACSL1 is increased in myeloid cells from individuals with systemic lupus erythematosus (SLE), an autoimmune condition characterized by increased IFN production. Taking advantage of a myeloid cell-targeted ACSL1-deficient mouse model and a series of lipidomics, proteomics, metabolomics and functional analyses, we show that IFN-I leverages induction of ACSL1 to increase accumulation of fully saturated phosphatidic acid species in macrophages. Conversely, ACSL1 induction is not needed for IFN-I's ability to induce the prototypical IFN-stimulated protein signature or to suppress proliferation or macrophage metabolism. Loss of ACSL1 in IFN-I stimulated myeloid cells enhances apoptosis and secondary necrosis in vitro, especially in the presence of increased saturated fatty acid load, and in a mouse model of atherosclerosis associated with IFN overproduction, resulting in larger lesion necrotic cores. We propose that ACSL1 induction is a mechanism used by IFN-I to increase phosphatidic acid saturation while protecting the cells from saturated fatty acid-induced cell death.PMID:39675509 | DOI:10.1016/j.jlr.2024.100730

Mol Metab. 2024 Dec 13:102082. doi: 10.1016/j.molmet.2024.102082. Online ahead of print.ABSTRACTIn white adipose tissue, disturbed creatine metabolism through reduced creatine kinase B (CKB) transcription contributes to obesity-related inflammation. However, the mechanisms regulating CKB expression in human white adipocytes remain unclear. By screening conditions perturbed in obesity, we identified endoplasmic reticulum (ER) stress as a key suppressor of CKB transcription across multiple cell types. Through follow-up studies, we found that ER stress through the IRE1-XBP1s pathway, promotes CKB promoter methylation via the methyltransferase DNMT3A. This epigenetic change represses CKB transcription, shifting metabolism towards glycolysis and increasing the production of the pro-inflammatory chemokine CCL2. We validated our findings in vivo, demonstrating that individuals living with obesity show an inverse relationship between CKB expression and promoter methylation in white adipocytes, along with elevated CCL2 secretion. Overall, our study uncovers a regulatory axis where ER stress drives inflammation in obesity by reducing CKB abundance, and consequently altering the bioenergetic state of the cell. (150 words).PMID:39675471 | DOI:10.1016/j.molmet.2024.102082

Microb Pathog. 2024 Dec 13:107228. doi: 10.1016/j.micpath.2024.107228. Online ahead of print.ABSTRACTBACKGROUND: Accumulating evidence suggests that gut microbiota (GM) is clearly associated with the pathogenesis of type 2 diabetes mellitus (T2DM). However, the underlying mechanism of GM dysbiosis participates the onset of T2DM is not fully understood. The spontaneous T2DM cynomolgus monkeys are a powerful model for understanding the pathological mechanism of T2DM.METHODS: Fecal samples were collected from 7 spontaneous T2DM cynomolgus monkeys and 7 healthy controls matched with similar age for multi-omics analysis, including shotgun metagenomic sequencing, untargeted metabolomics profiling, and targeted metabolomics focusing on short chain fatty acids (SCFAs). Lastly, the correlation network between differential gut microbial species and fecal metabolites was performed to explore the potential biomarkers of T2DM.RESULTS: We found that 17 low-abundance species showed significant differences between the two groups. Analysis of gut microbial functions revealed that 16 KEGG pathways and 51 KEGG modules were significantly different in the two groups. Meanwhile, 276 fecal DEMs were identified, and these DEMs were enriched in the KEGG pathways, including Nucleotide metabolism, ABC transporters, Purine metabolism and so on. Lastly, Spearman correlation network analysis showed that the species of Anaerostipes_hadrus and Lachnoanaerobaculum_umeaense, and the metabolites including Glycerophospho-N-palmitoyl ethanolamine and 2-Hydroxycinnamic acid might serve as potential biomarkers of T2DM.CONCLUSIONS: Our study provides novel insights into specific alterations in the GM composition, gene functions, and fecal metabolic profiles in spontaneous T2DM cynomolgus monkeys.PMID:39675442 | DOI:10.1016/j.micpath.2024.107228

Neurocirugia (Astur : Engl Ed). 2024 Dec 13:S2529-8496(24)00082-0. doi: 10.1016/j.neucie.2024.12.004. Online ahead of print.ABSTRACTBACKGROUND AND OBJECTIVE: Chronic subdural hematoma is one of the most common diseases in neurosurgical practice. The content of electrolytes and gases in the collection could participate in the growth and expansion mechanism, however, there is no evidence that they have been studied before. The objective has been to identify electrolyte, gas and internal metabolomic markers of the content of chronic subdural hematomas, with the possibility of participating in their growth and expansion and to substantiate a pathophysiological hypothesis that interacts with existing ones.MATERIAL AND METHOD: A descriptive study was carried out with 53 patients operated on for chronic subdural hematoma, at the "Roberto Rodríguez Fernández" General Teaching Hospital of Morón in Ciego de Ávila, Cuba, in the period between January 2019 and December 2023. The diagnoses were obtained with computed axial tomography. The electrolyte and blood gas components of hematomas are correlated with clinical and neuroimaging variables.RESULTS: Patients over 70 years of age predominated, 37 (69.81%) and males 38 (71.70%). The Markwalder scale upon admission showed a predominance of Grade III in 24 cases (45.28%). The Glasgow outcome scale showed a predominance of Grade V, 31 (58.49%).CONCLUSIONS: Electrolyte and gasometric metabolomic markers of subdural blood can promote the phenomenon of progressive growth and expansion and have a synergistic effect with the rest of the pathophysiological mechanisms.PMID:39675425 | DOI:10.1016/j.neucie.2024.12.004

Food Chem. 2024 Dec 5;468:142391. doi: 10.1016/j.foodchem.2024.142391. Online ahead of print.ABSTRACTUlcerative colitis (UC) is a recurrent intestinal disease caused by a complex of factors, and there are serious adverse effects and tolerance problems associated with the current long-term use of therapeutic drugs. The development of natural food sources and multi-targeted drugs for the treatment of UC is imminent. Portulaca oleracea L. (PO), as a vegetable, has been shown in studies to have an anti-UC effects. However, the relationship between the abundant active ingredients contained in Portulaca oleracea L. and the improvement of intestinal barrier, gut microbiota and metabolites is unclear. In the present study, Portulaca oleracea L. which was found to be rich in phenolic acid-based active ingredients, were effective in alleviating dextran sulfate sodium (DSS)-induced body weight loss, disease activity index (DAI) score and colon length in mice. It also decreased C-reactive protein (CRP) and myeloperoxidase (MPO) responses, reduced the permeation of fluorescein isothiocyanate (FITC)-dextran, lipopolysaccharide (LPS) and evans blue (EB), and improved histopathological scores. Meanwhile, in vitro and in vivo validation revealed the protective effects of purslane on the intestinal barrier indicators ZO-1, Occludin and Claudin-1, and inhibited the expression of inflammation-associated iNOS and NLRP3 proteins through the NF-κB signaling pathway. In addition, purslane increased the diversity of the intestinal flora, enhancing the proportion of the genera Butyricoccus, Dorea and Bifidobacterium and decreasing the percentage of Bacteroides, Turicibacter and Parabacteroides. Serum metabolomics analysis showed that the imbalance of 39 metabolites was significantly reversed after PO deployment. Enrichment analysis showed that Pentose phosphate pathway and Pyruvate metabolism pathway were the key pathways of PO against UC. Overall, purslane effectively improved the intestinal barrier disruption and intestinal inflammation by inhibiting the NF-κB signaling pathway, and adjusted the disorder of gut microbiota and metabolites to exert anti-UC effects.PMID:39675274 | DOI:10.1016/j.foodchem.2024.142391

Ultrason Sonochem. 2024 Dec 13;112:107200. doi: 10.1016/j.ultsonch.2024.107200. Online ahead of print.ABSTRACTIschemia brain injury is closely associated with the gut microbiota. Polysaccharides, as a typical prebiotic, have been extensively employed in stroke treatment. In our previous study, Pueraria lobata polysaccharide (PLP-3) with antioxidant activity was prepared via water extraction and alcohol precipitation combined with ultrasonic degradation. In this study, the effects of PLP-3 on ischemia brain injury and its regulatory effects on the gut microbiota were further investigated. The results demonstrated that PLP-3 effectively reduced the infarct area, improves neurological function, and alleviates neuronal damage of cerebral ischemia injury. Mechanistically, PLP-3 significantly reduces serum LPS levels in MCAO mice, inhibiting TLR-4 activation in brain tissue and thereby reducing IL-1β and TNF-α levels. Meanwhile, PLP-3 significantly repaired the intestinal barrier injury by increasing the expression of tight junction proteins (ZO-1 and Occludin) and increasing the number of goblet cells. Additionally, the structure and composition of gut microbiota in MCAO mice after PLP-3 intervention, were also significantly changed, especially the enrichment of Lactobacillus and the reduction of Corynebacterium and Staphylococcus. At the same time, short chain fatty acid, metabolites of gut microbiota, were also significantly increased and significantly correlated with the abundance of Lactobacillus. Moreover, LC-MS untargeted metabolomics revealed that PLP-3 significantly improves the intestinal metabolic profile after cerebral ischemia injury, upregulating the amino acid biosynthesis pathway and enriching amino acids such as glutamine and arginine, as well as neuroprotective flavonoids such as fisetin and liquiritigenin. These results suggested that PLP-3 could protect mice from cerebral ischemia-reperfusion injury by regulating gut microbiota and repairing gut barrier, inhibiting brain LPS/TLR4/MyD88 inflammatory pathway, therefore we provide a theoretical basis for PLP-3 as a functional food to prevent ischemic brain injury.PMID:39675265 | DOI:10.1016/j.ultsonch.2024.107200

Int J Food Microbiol. 2024 Dec 10;429:111019. doi: 10.1016/j.ijfoodmicro.2024.111019. Online ahead of print.ABSTRACTElaeagnus moorcroftii Wall. ex Schlecht (EWS) as a suitable food matrix contains abundant flavonoids for promoting human health, this study aimed to use flavonoid-targeted metabolomics and transcriptome sequencing to investigate the transformation of flavonoids in EWS juice (EWSJ) by mono- and mixed-cultures fermentations of Bifidobacterium animalis subsp. lactis HN-3 (B.an3) and Lacticaseibacillus paracasei YL-29 (L.cp29). A total of 33 flavonoids were identified in mono- and mixed-cultures fermented EWSJ. Among them, fermentation by B.an3 produced specific deglycosylation products (kaempferol (17.6 mmol/L) and luteolin (4.5 mmol/L)) and methoxylation products (syringaldehyde (59.05 mmol/L)), and fermentation by L.cp29 resulted in a specific deglycosylation product (quercetin (9.2 mmol/L)). The co-culture fermentation further increased the levels of isorhamnetin (52.3 mmol/L), and produced a specific product (homoplantaginin (0.03 mmol/L)), which significantly increased the bioactive-form flavonoids. Moreover, we analyzed changes in different flavonoid metabolites and differential genes before and after fermentation. After L.cp29 fermentation the expression of glycoside hydrolases and oxidoreductases were increased compared to other groups. After B.an3 fermentation the expression of isomerases and synthetases were increased compared to other groups. In particular, 6-phosphogluconolactonase (Pgl) and glucose-6-phosphate isomerase (Pgi) were increased in B.an3 fermentation. Thus, we validated the predicted transformation reactions by the biotransformation of flavonoids by the collected strains and crude enzyme extracts of B.an3 and L.cp29. These findings provided a basis for the development of functional plant-based foods with enhanced bioactive flavonoids.PMID:39675163 | DOI:10.1016/j.ijfoodmicro.2024.111019

Ecotoxicol Environ Saf. 2024 Dec 14;290:117460. doi: 10.1016/j.ecoenv.2024.117460. Online ahead of print.ABSTRACTAmmonium (NH₄⁺) is a primary nitrogen source for many species, yet NH₄⁺-rich wastewater presents a substantial risk to environment. Chlorella sorokiniana is widely recognized for wastewater treatment. The development of high NH₄⁺ tolerant strains has the potential to significantly enhance wastewater treatment efficiency and reduce treatment costs. This study reports the identification of a C. sorokiniana strain designated hact (high ammonium concentration tolerance). This strain demonstrates a remarkable tolerance to NH₄⁺ (1000 mg/L). Integrative analyses of physiology, metabolomics, and transcriptomics demonstrated that transport inhibition is the principal resistance mechanism against high NH₄⁺ stress in C. sorokiniana. Notably, under elevated NH₄⁺ conditions, the hact strain maintained robust intracellular homeostasis. In contrast, the wild-type (WT) strain exhibited suppressed metabolic activity, reactive oxygen species (ROS), and an excess of detrimental metabolites such as amines. This research enriches our understanding of microalgal molecular responses to high NH₄⁺ stress, paving the way for the development of engineered optimization strategies for microalgal bioremediation systems treating NH₄⁺-rich wastewater.PMID:39675076 | DOI:10.1016/j.ecoenv.2024.117460

Metabolomics. 2024 Dec 14;21(1):5. doi: 10.1007/s11306-024-02200-4.ABSTRACTINTRODUCTION: Inflammatory bowel diseases (IBDs) are chronic immune driven intestinal disorders with marked metabolic alteration. Mass spectrometry imaging (MSI) enables the direct visualization of biomolecules within tissues and facilitates the study of metabolic changes. Integrating multiple spatial information sources is a promising approach for discovering new biomarkers and understanding biochemical alteration within the context of the disease.OBJECTIVE: This study evaluates the metabolomic changes in gut tissue samples from a preclinical model of spontaneous colitis, the HLA-B27/hβ2m transgenic rat, to uncover disease biomarkers.METHODS: We applied MSI to study the biochemical profile of bowel samples from HLA-B27/hβ2m transgenic and WT control rats in an unbiased manner. Statistical comparison was used to identify discriminative features. Some features were annotated using LC-MS/MS. The significance of these discriminative features was evaluated based on their distribution within histological layers and the presence of immune infiltration.RESULTS: We identified spatially resolved changes in the metabolomic pattern of HLA-B27+ samples compared to WT controls. Out of the 275 discriminative features identified, 83 were annotated as metabolites. Two functional groups of discriminative metabolites were discussed as markers of gut barrier impairment and immune cell infiltration.CONCLUSION: MS imaging's spatial dimension provides insights into disease mechanisms through the identification of spatially resolved biomarkers.PMID:39674857 | DOI:10.1007/s11306-024-02200-4

Int J Biol Macromol. 2024 Dec 12:138755. doi: 10.1016/j.ijbiomac.2024.138755. Online ahead of print.ABSTRACTUlcerative colitis (UC) is a relapsing disease with an increasing morbidity and prevalence. Dietary polysaccharides have recently become a research hotspot because of their therapeutic effects and safety on UC. Our previous research elucidated that pectic polysaccharide from Phyllanthus emblica L. (PEP-1) could alleviate dextran sodium sulfate-induced UC mice. Herein, metabolomics and transcriptomics were further applied to disclose the underlying mechanisms behind PEP-1's anti-inflammatory effects. PEP-1 intervention altered the serum metabolite contents and pathways represented by decreasing xanthine and sphinganine levels. Changes in gene expressions correlated with metabolite variations led by the suppression of the expression of the inflammatory factors, colorectal cancer promoter, and NF-κB pathway as well as the enhancement of tight junctions. This study demonstrated that the ameliorating effect of chronic UC was partially ascribed to the alteration of the serum metabolites and changes in gene expression.PMID:39674473 | DOI:10.1016/j.ijbiomac.2024.138755