MetaboLights

application/xml

ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/m_MTBLS15265_LC-MS_negative_hilic_metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/m_MTBLS15265_LC-MS_positive_hilic_metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/a_MTBLS15265_LC-MS_negative_hilic_metabolite_profiling.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/s_MTBLS15265.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/a_MTBLS15265_LC-MS_positive_hilic_metabolite_profiling.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ21.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ03.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ25.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/QC3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ11.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/QC5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ12.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ04.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ24.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ24.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ02.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ15.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/QC4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ14.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ03.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ23.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ11.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ01.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/QC2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ05.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ22.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/QC4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ15.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ01.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ13.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/QC3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ02.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/QC1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ23.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ22.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ04.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ21.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ13.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/QC1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ12.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ14.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/QC5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/ZLJ25.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/neg/QC2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265/FILES/RAW_FILES/pos/ZLJ05.rawprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS15265Basic filtering of each metabolite was performed based on parameters such as retention time and mass-to-charge ratio. Then, retention time deviation was set at 0.2 min and mass deviation at 5 ppm for peak alignment across different samples to improve identification accuracy. Subsequently, peak extraction was conducted by setting the mass deviation at 5 ppm, signal intensity deviation at 30%, signal-to-noise ratio at 3, minimum signal intensity, and adduct ion information. Peak areas were quantified, and target ions were integrated. Predict molecular formulas using molecular ion peaks and fragment ions, and compare with the mzCloud (https://www.mzcloud.org), mzVault and Masslist databases. Remove background ions using blank samples. Normalize the original quantitative results using the formula: sample original quantitative value / (sample metabolite quantitative value total / QC1 sample metabolite quantitative value total) to obtain relative peak areas. Compounds with a CV greater than 30% of the relative peak area in the QC sample were removed. Finally, the identification and relative quantification results of the metabolites were obtained. The data processing was based on the Linux operating system (CentOS version 6.6) and the software R and Python.MetaboLightsPublicLiquid Chromatography MS - positive - hilicLiquid Chromatography MS - negative - hilicThe LC analysis was performed on a Vanquish UHPLC System (Thermo Fisher Scientific, USA). Chromatography was carried out with an ACQUITY UPLC HSS T3 (150 x 2.1 mm, 1.8 μm) (Waters, Milford, MA, USA). The column maintained at 40 °C. The flow rate and injection volume were set at 0.25 mL/min and 2 μL, respectively. For LC-ESI (+)-MS analysis, the mobile phases consisted of (C) 0.1% formic acid in acetonitrile (v/v) and (D) 0.1% formic acid in water (v/v). Separation was conducted under the following gradient: 0.0-1.0 min, 2% C; 1.0-9.0 min, 2-50% C; 9.0-12.0 min, 50-98% C; 12.0-13.5 min, 98% C; 13.5-14.0 min, 98-2% C; 14.0-20.0 min, 2% C. For LC-ESI (-)-MS analysis, the analytes was carried out with (A) acetonitrile and (B) ammonium formate (5 mM). Separation was conducted under the following gradient: 0.0-1.0 min, 2% A; 1.0-9.0 min, 2-50% A; 9.0-12.0 min, 50-98% A; 12.0-13.5 min, 98% A; 13.5-14.0 min, 98-2% A; 14.0-17.0 min, 2% A.Microbiota network module-derived tryptophan metabolites promote cognitive improvement via microglial modulation.Yuxiang PanZhejiang University of Technologyhippocampusmass spectrometry assay1. Accurately weigh an appropriate amount of sample into a 2 mL centrifuge tube, add 1000 μL tissue extract (75% 9:1 methanol: chloroform, 25% H2O), add 3 steel balls.2. Put it into the tissue grinder, grind it at 50 Hz for 60 s, and repeat the above operation twice.3. Room temperature ultrasound for 30 min and ice bath for 30 min.4. Centrifuge for 10 min at 12,000 rpm and 4 °C, take all the supernatant, transfer it to a new 2 mL centrifuge tube, concentrate and dry it.5. Accurately add 200 μL 50% acetonitrile solution is prepared with 2-Amino-3-(2-chloro-phenyl)-propionic acid (4 ppm) (stored at 4 °C) to re dissolve the sample, filter the supernatant by 0.22 μm membrane and transfer into the detection bottle for LC-MS detection.Mus musculushttps://www.ebi.ac.uk/metabolights/MTBLS15265Yuxiang Pan. College of Biotechnology and Bioengineering, Zhejiang University of Technology. No.6 District, Zhaohui, Hangzhou, Zhejiang, 310032, China. 18067067598@163.com. 18868724938.The offline data (.raw files) were imported into the CD 3.1 database search software for processing. Treatment groupEFO18067067598@163.comAfter sacrificing the mice, dissect and isolate the hippocampal tissue, then store it in a -80 °C freezer.MetabolomicsThermo Scientific Vanquish UHPLC Systemultra-performance liquid chromatography-mass spectrometrypooled quality control sampleMus musculusMicrobiotaThermo Scientific Q Exactivehippocampusuntargeted analysisuntargeted metabolitesexperimental sampleThermo Scientific Vanquish UHPLC Systemultra-performance liquid chromatography-mass spectrometrypooled quality control sampleMus musculusMicrobiotaThermo Scientific Q Exactivehippocampusuntargeted analysisuntargeted metabolitesexperimental sampleMass spectrometric detection of metabolites was performed on Q Exactive (Thermo Fisher Scientific, USA) with ESI ion source. Simultaneous MS1 and MS/MS (Full MS-ddMS2 mode, data-dependent MS/MS) acquisition was used. The parameters were as follows: sheath gas pressure, 30 arb; aux gas flow, 10 arb; spray voltage, 3.50 kV and -2.50 kV for ESI(+) and ESI(-), respectively; capillary temperature, 325 °C; MS1 range, 81-1000 m/z; MS1 resolving power, 70000 FWHM; number of data dependant scans per cycle, 10; MS/MS resolving power, 17500 FWHM; normalized collision energy, 30%; dynamic exclusion time, automatic.OxyphencyclimineD-Glucuronic Acid2-Furoate1-Hexadecylthio-2-hexadecanoylamino-1,2-dideoxy-sn-glycero-3-phosphocholinePhosphoglycolic acidgamma-Aminobutyric acidGuaiacolAminoglutethimideN-a-AcetylcitrullineEctoineN1,N12-DiacetylspermineQuinolineKinetinHeptanoic acidgamma-Glutamyl-beta-cyanoalanineNicotinate D-ribonucleosideCholest-4-en-3-one2-Methylbenzoic acid6-Hydroxyhexanoic acid3-Methyl-3-hydroxypentanedioateOxoglutaric acidCitrulline4,4'-Dihydroxy-alpha-methylstilbene(R)-mandelic AcidFluroxypyr5-Hydroxyindoleacetic acidCarbofuran1-HexadecanolHydroxykynurenineCyclohexylaminePilocarpineGriseofulvin1,2,3-TrihydroxybenzeneN2-Succinyl-L-ornithineUreidopropionic acidCannabinolHordenineN6-(L-1,3-Dicarboxypropyl)-L-lysineMevalonic acidOleic acidGlutaric acid5-Hydroxymethyl-2-furaldehyde(R)-PantolactoneAdenylsuccinic acid7-DehydrodesmosterolN-Acetylglutamic acidMoupinamideN2-Succinyl-L-glutamic acid 5-semialdehydePentazocineLimonene-1,2-diolGlutarate semialdehydeIsoetharineN-Acetylneuraminic acid2-Oxo-4-methylthiobutanoic acidLevetiracetam4-Pyridoxic acidDimethenamid3,3'-Dimethoxybenzidine6-BenzylaminopurineAmiodaroneAscorbate7-MercaptoheptanoylthreonineADPIndoleacetaldehydeNudicauline2,4-Diaminoanisole25-Hydroxycholesterol2-Biphenylol4-Acetamido-2-aminobutanoic acid6-Hydroxytryprostatin BApioleOrbencarbL-3-CyanoalanineMidodrine(R) 2,3-Dihydroxy-3-methylvaleratetrans-trans-Muconic acidN-Nitrosodi-n-butylamineDichlorvos(S)-2-PropylpiperidineProfenofos1,3-BenzenediolOrnithineRetinalN-Acetylaspartylglutamic acidL-threo-3-Methylaspartate4-HydroxyphenylacetaldehydeMesnaIndoledTDP-6-deoxy-beta-L-talose5-Methyl-2-furancarboxaldehyde4-Methylbenzaldehyde3-SulfinoalanineBenzamidegamma-L-Glutamyl-D-alanineIsocitric acidBupivacaineMelphalanPyroquilon3-Indoleacetonitrile(5-L-Glutamyl)-L-glutamateL-CarnitineCeruleninMalonyl-CoAThiamine(6S)-6-beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotideD-LysopineLauroyl-CoAPropoxur9-OxoODEAcetylphosphate3-Dehydroshikimate2-Hydroxycinnamic acidGuanidoacetic acidL-Dopa1-NaphthylamineArgininosuccinic acid3-Methyl-L-tyrosineS-Carboxymethyl-L-cysteineL-Phenylalanine1-DeoxynojirimycinDocosahexaenoic acid(R)-AmphetamineEucalyptol1-HydroxymethylnaphthalenePropanoyl phosphate2-Pyrocatechuic acidSpermidineTriethylamineDimethyl trisulfide2-Naphthylamine2-Hexaprenyl-6-methoxy-1,4-benzoquinone2,5-DioxopentanoateQuinonePrecorrin 1L-IditolIsoprothiolaneThiotepaTetracenomycin EL-ProlinamideClotrimazolePhenylacetaldehydeIndolebutyric acidN(6)-Methyllysinepara-Phenylenediamine3-aci-NitropropanoateTabernamineCurcumenolCefradinegamma-L-Glutamyl-L-cysteine5-HydroxyindoleacetaldehydeAminomalonic acid(S)-4-HydroxymandelateRifampicinTropatem-CresolDehydrocostus lactoneNADPPhenmetrazinePhenthoateFlunisolidePimelic acidDesaminotyrosineCarbazoleThiamine aldehyde5-Hydroxypentanoic acidFormiminoglutamic acidGlycyl-leucineProtoveratrine BFipronilThiabendazoleAtrazinePipecolic acidItaconic acidGlucose 6-phosphateBetaine1-Hydroxy-2-naphthoateN-MethylhydantoinPhenacetinN-Phenyl-2-naphthylamineAMPLotaustralinbeta-Alanyl-L-arginineTrientinePelargonidinMonomethyl sulfateOxymetazolineL-Methionine S-oxideCytidineHydroquinoneDyphyllineBisphenol AN-Acetyl-L-aspartic acidgamma-GlutamylalanineL-Glutamic acid 5-phosphate4-OxoglutaramateDolichothelineN-AcetylaspartylglutamylglutamateL-LysineLetrozole(S)-2-MethylmalateLeucodopachromeVardenafilPyrrolidonecarboxylic acidPropylthiouracil1-MethylhistidineDodecanoic acidNorethindroneCloransulam-methyl2-Amino-2-deoxy-D-gluconate2-Hydroxy-3-oxoadipateThiocyclamEthoprophoscis-Aconitic acid(S)-Abscisic acidFluorouracilThymineNootkatoneVincristinePelargonic acidPymetrozine4,5-Dihydroorotic acidD-RiboseMaltolPiperocaine(R)-HigenamineIsonicotinic acidSorbitolTaurineValpromideAllantoinDapsoneO-PhosphoethanolamineLoratadine(R)-2-O-SulfolactateThiamine pyrophosphateProcymidonePirbuterol2-Hydroxyadipic acidKynurenic acidL-Leucinebeta-Carotenegamma-Glutamyl-beta-aminopropiononitrileAnabasine(R)-4-HydroxymandelateBarbituric acidSinapineStyrene OxideCatecholLeukotriene E4Nalbuphine4-OxoprolineMinovincinineAntibiotic JI-20A11-Aminoundecanoic acidUndecanoic acidGabapentinCitrininPyrrole-2-carboxylic acidA alpha CPrilocaine(R)-Methylmalonate semialdehydeNeostigmineUrateSe-MethylselenocysteineThiamethoxamD-Phenyllactic acid4-IsopropylbenzaldehydeN-Acetyl-a-neuraminic acidTetracaineNiacinamideSerotoninGlycineamideribotideIsopyridoxalPQQ5'-Oxoinosine1H-Indole-3-acetamideHexylaminecis-4-Hydroxy-L-prolineUracilD-4'-PhosphopantothenateL-KynurenineAminocaproic acid2,3-Diaminopropionic acid2-MethylserineAzacitidinePelargonidin 3-O-3'',6''-O-dimalonylglucosideCytosinepsi-Pelletierine(Z)-But-1-ene-1,2,4-tricarboxylateDihydro-O-methylsterigmatocystinParathion-methylSertraline5-(Methylthio)-2,3-dioxopentyl phosphate(3S,5S)-Carbapenam-3-carboxylic acidCoumarinL-Malic acidGentamicin C1aSpermineSuccinic acidHypoxanthineBuforminPelletierineStrophanthidinL-ArgininePermethrinLevallorphan5-Methylbarbituratep-CymeneDiosminBovinocidinHomovanillic acid1,1-DimethylbiguanideL-Cysteine4,4'-Methylene-bis-(2-chloroaniline)5-Carboxy-2-pentenoyl-CoASalanninCephalomannineL-Glutamic acidS-(Hydroxymethyl)glutathioneTropine(E)-MonocrotophosHomocitrullinedAMP2-HydroxyphenethylamineL-Serine1D-1-Guanidino-3-amino-1,3-dideoxy-scyllo-inositolBeta-Guanidinopropionic acidImidazol-5-yl-pyruvatePromethazineNeohesperidin4,4'-Methylene bis(2-methylaniline)SubaphyllineAnserineUreidosuccinic acid4-Hydroxycinnamic acid2-HeptanoneD-4-Hydroxy-2-oxoglutarateTyramineBerberineTetrahydropteridinedTDP-3-N,N-dimethylamino-2,3,6-trideoxy-4-keto-D-glucoseN,N-DiethylbenzeneacetamidePyraflufen-ethyl4-Hydroxybenzoic acidN-Formyl-L-methioninep-Hydroxyphenylacetic acidVanylglycolL-MethionineCiliatineN-AcetyldemethylphosphinothricinCysteinylglycineN-Acetyl-D-Glucosamine 6-PhosphateDicambaGlycerophosphocholineErgothioneine1-Aminocyclopropanecarboxylic acidNalidixic Acid5-(2-Hydroxyethyl)-4-methylthiazole(+)-NorephedrineN-AcetylornithinePropazineAspartylglycosamineSuccinic acid semialdehydeSkatoleHemeMannitolS-Glutathionyl-L-cysteineBetaine aldehydePyridoxamine4-HydroxycinnamoylagmatineSalicylic acidN-AcetylhistidinePhosphoenolpyruvic acid3,4-MethylenedioxyamphetamineAfzelechinRilmenidineN-AcetylputrescineMagnololMannitol 1-phosphateAndrosteroneXanthine(-)-Epigallocatechin3-[(1-Carboxyvinyl)oxy]benzoateL-GlutamineAcetylcholineepsilon-CaprolactoneDihydromacarpineCapsidiolDelphinidin 3-rutinosideAcetylcysteine2-Caffeoylisocitrate5-HydroxymethyluracilTranexamic AcidDiphenylamineOrotic acid3-Phosphoglyceric acidUDPBenzaldehyde1-Pyrroline-2-carboxylic acidFarnesoic acid20-Hydroxyecdysone10-HydroxycarbazepineMethyl (indol-3-yl)acetatePhosphorylcholineOmethoateIminoarginineAminophenazoneL-Aspartic acidProcaineN-Methyl-D-aspartic acidSedoheptuloseN-Alpha-acetyllysineL-Targinine2-MethylthiobenzothiazoleLeucocyanidin2,3-ButanediolMedroxyprogesteroneCamalexinMiltironeEpsilon-caprolactamUDP-N-acetyl-D-mannosamineL-2-Hydroxyglutaric acidPelargonidin 5-O-beta-D-glucoside 3-O-beta-D-sambubiosideBaicalinFe-coproporphyrin IIIChlorpyrifosEpinephrineMefloquineAtazanavir(-)-alpha-CurcumeneAndrosta-1,4-diene-3,17-dione3,4-DihydroxyphenylglycolN-Methyl-L-glutamic acid3'-AMPPhosphocreatine4-Methylumbelliferone glucuronideCarbamoyl phosphateEstronefalseMicrobiota network modules-derived tryptophan metabolites improve cognition via microglial AhR/Sirpα signalingGut microbiota dysbiosis has emerged as one of the hallmarks of aging, highlighting the need to identify microbial network modules as new biomarkers rooted in microbiota interactions and develop targeted nutritional interventions. The current research, integrating data from Alzheimer's disease (AD) patient cohorts, meta-analysis, and animal experiments, identified 4 core bacterial genera modules associated with aging and cognition. The combination of Bacteroides thetaiotaomicron, Lachnospiraceae bacterium, and Roseburia intestinalis was positively correlated with neurofunction and significantly improved cognitive performance in LPS-induced and AD mice. Metabolomic profiling revealed disrupted tryptophan metabolism in aging mice, which was restored upon intervention with the core bacterial strains. Mechanistically, tryptophan metabolites activated the aryl hydrocarbon receptor (AhR) in the hippocampus, modulating microglial phagocytosis via Sirpα and Trem2 signaling. Moreover, sesaminol enhanced cognitive function by modulating specific modules. These findings elucidated the role of the microbiota-tryptophan metabolites-microglia axis in anti-aging and provided new directions for microbiota-targeted interventions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