MetaboLights

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ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12751/m_MTBLS12751_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12751/m_MTBLS12751_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12751/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12751/s_MTBLS12751.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12751/a_MTBLS12751_LC-MS_negative_reverse-phase_metabolite_profiling.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12751/a_MTBLS12751_LC-MS_positive_reverse-phase_metabolite_profiling.txtprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12751brainThe metabolites were identified by searching database, and the main databases were the HMDB (http://www.hmdb.ca/), Metlin ( https://metlin.scripps.edu/) and Majorbio Database .mass spectrometry assayBriefly, Whole brain samples were homogenized, and 50 mg of tissue was extracted using 400 μL of extraction solution (methanol : double-distilled water, 4:1, v/v) containing 0.02 mg/mL internal standard (L-2-chlorophenylalanine). The tissue was ground using a frozen tissue grinder for 6 min (− 10 ℃, 50 Hz) followed by low-temperature ultrasonic extraction for 30 min (5 ℃, 40 KHz). Samples were then incubated at −20 ℃ for 30 minutes, centrifuged at 4 ℃ at 13000 × g for 15 minutes, and the supernatant was transferred to sample vials with inner retractable tubes for LC-MS analysis.Mus musculusThe pretreatment of LC/MS raw data was performed by Progenesis QI (Waters Corporation, Milford, USA) software, and a three-dimensional data matrix in CSV format was exported. The information in this three-dimensional matrix included: sample information, metabolite name and mass spectral response intensity. Internal standard peaks, as well as any known false positive peaks (including noise, column bleed, and derivatized reagent peaks), were removed from the data matrix, deredundant and peak pooled.Treatmenthttps://www.ebi.ac.uk/metabolights/MTBLS12751mxzheng@xzhmu.edu.cnThe effects of chronic olanzapine treatment on cognitive function: after habituation to the laboratory environment for 1 week, the 8-week-old female mice were matched by body weight and randomly divided into two groups: 1) the control group mice were fed a lab chow diet; 2) the olanzapine (OLZ) group mice were fed a lab diet supplemented with olanzapine (50 mg olanzapine per 1 kg lab chow diet ). All groups received their interventions for 9 weeks. At the end of the experiment, mice were anesthetized with sodium pentobarbitone and sacrificed following final measurements.Brain tissues were collected and stored at -80 ℃ for further analyses.MetaboLightsPublicMetabolomicsLiquid Chromatography MS - negative - reverse phaseLiquid Chromatography MS - positive - reverse phaseultra-performance liquid chromatography-mass spectrometryThermo Scientific Vanquish UHPLC SystemMus musculustandem mass spectrometryuntargeted analysisThermo Scientific Q Exactive HF-Xuntargeted metabolitesbrainThe LC-MS/MS analysis of sample was conducted on a Thermo UHPLC-Q Exactive HF-X system equipped with an ACQUITY HSS T3 column (100 mm × 2.1 mm, 1.8 μm) at Majorbio Bio-Pharm Technology Co. Ltd. (Shanghai, China). The mobile phases consisted of 0.1% formic acid in water:acetonitrile (95:5, v/v) (solvent A) and 0.1% formic acid in acetonitrile:isopropanol:water (47.5:47.5, v/v) (solvent B). Positive ion mode separation gradient: 0-3 min, mobile phase B was increased from 0% to 20%; 3-4.5 min, mobile phase B was increased from 20% to 35%; 4.5-5 min, mobile phase B was increased from 35% to 100%; 5-6.3 min, mobile phase B was maintained at 100%; 6.3-6.4 min, mobile phase B was decreased from 100% to 0%; 6.4-8 min , mobile phase B was maintained at 0%. Separation gradient in negative ion mode: 0-1.5 min, mobile phase B rises from 0 to 5%; 1.5-2 min, mobile phase B rises from 5% to 10%; 2-4.5 min, mobile phase B rises from 10% to 30%; 4.5-5 min, mobile phase B rises from 30% to 100%; 5-6.3 min, mobile phase B linearly maintains 100%; 6.3-6.4 min, the mobile phase B decreased from 100% to 0%; 6.4-8 min, the mobile phase B was linearly maintained at 0%. The flow rate was 0.40 mL/min and the column temperature was 40℃.Gut Microbiota–Derived Ergothioneine Alleviates Antipsychotic-Induced Synaptic and Cognitive Impairments.Thermo Scientific Vanquish UHPLC Systemultra-performance liquid chromatography-mass spectrometryMus musculustandem mass spectrometryuntargeted analysisThermo Scientific Q Exactive HF-Xuntargeted metabolitesbrainMingxuan ZhengXuzhou Medical UniversityThe mass spectrometric data were collected using a Thermo UHPLC-Q Exactive HF-X Mass Spectrometer equipped with an electrospray ionization (ESI) source operating in positive mode and negative mode. The optimal conditions were set as followed: source temperature at 425℃ ; sheath gas flow rate at 50 arb; Aux gas flow rate at 13 arb; ion-spray voltage floating (ISVF) at -3500V in negative mode and 3500V in positive mode, respectively; Normalized collision energy , 20-40-60V rolling for MS/MS. Full MS resolution was 60000, and MS/MS resolution was 7500.falseGut Microbiota–Derived Ergothioneine Alleviates Antipsychotic-Induced Synaptic and Cognitive ImpairmentsBackground: Chronic use of antipsychotic drugs is associated with neuronal damage and cognitive impairment, potentially mediated by alterations in gut microbiota metabolites, although the specific metabolite involved remains unknown.Objective: To identify the key metabolite responsible for antipsychotic-induced synaptic and cognitive impairment and assess the potential for its reversal through targeted supplementation.Design: Mice were chronically treated (8 weeks) with olanzapine, risperidone, or clozapine. In the olanzapine model, gut microbiota (16S rRNA and shotgun metagenomic sequencing) and metabolites (untargeted metabolomics) were analyzed, identifying ergothioneine depletion, validated in olanzapine-treated patients. Causality was tested via fecal microbiota transplantation (FMT) and ergothioneine supplementation. Neuronal-specific PTP1B knockout mice elucidated mechanistic pathways.Results: Chronic olanzapine treatment caused gut microbial dysbiosis, disrupted intestinal barrier integrity, and impaired cognitive function in mice. A key finding was the depletion of ergothioneine, the gut microbiota-derived metabolite, in both the blood and brain of mice, and in the blood of patients receiving olanzapine. This depletion was associated with a loss of ergothioneine-producing Cyanobacteria and subordinate taxa. Similar ergothioneine depletion and cognitive impairments were observed in risperidone- and clozapine-treated mice. Ergothioneine supplementation or FMT effectively prevented olanzapine-induced cognitive and synaptic impairments. Mechanistically, ergothioneine attenuated olanzapine-induced hippocampal oxidative stress and inhibited the redox-sensitive phosphatase PTP1B. Furthermore, neuronal- or hippocampal neuronal-specific deletion of PTP1B abolished olanzapine-induced synaptic and cognitive impairments. Conclusions: The significant reduction of ergothioneine induced by antipsychotic treatment leads to cognitive impairment, highlighting gut microbiota-derived metabolites as potential therapeutic targets for improving cognitive function in patients undergoing antipsychotic therapy.2026-04-082025-07-20MTBLS12751