MetaboLights

application/xml

ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13401/m_MTBLS13401_GC-MS_positive__metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13401/m_MTBLS13401_LC-MS_alternating_reverse-phase_metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13401/s_MTBLS13401.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13401/a_MTBLS13401_LC-MS_alternating_reverse-phase_metabolite_profiling.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13401/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13401/a_MTBLS13401_GC-MS_positive__metabolite_profiling.txtprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13401An MS-Omics in-house annotation and curation pipeline written in MATLAB (2022b, MathWorks) was applied. Identification of compounds was performed at four levels: Level 1: identification by retention times (compared against in-house authentic standards, with an accepted deviation of 0.2 min), accurate mass (with an accepted deviation of 3 ppm), and MS/MS spectra (with a match factor above 60). Level 2a: identification by retention times (compared against in-house authentic standards, with an accepted deviation of 0.2 min), accurate mass (with an accepted deviation of 3 ppm). Level 2b: identification by accurate mass (with an accepted deviation of 3 ppm), and MS/MS spectra from in-house authentic standards and mzCloud (ThermoScientific) at a match factor >60. Level 3: identification by accurate mass alone (with an accepted deviation of 3ppm), based on the Human metabolome database (v 5.0)[1]. In the case of known isotopes with indistinguishable retention time and fragmentation behaviour, co-eluting peaks were manually integrated and reported as compound groups (e.g. hexoses or sugar alcohols). Ref:[1] Wishart DS, Guo AC, Oler E, et al., HMDB 5.0: the Human Metabolome Database for 2022. Nucleic Acids Res. 2022. Jan 7;50(D1):D622–31. 34986597 MetaboLightsPublicLiquid Chromatography MS - alternating - reverse-phaseGas Chromatography MS - positiveSemi-polar metabolite profiling was performed by MS-Omics (part of cmbio, Vedbæk, Denmark). The semi-polar analysis in randomized order via reverse phase UHPLC was performed using an adapted version of the protocol previously described[1]. A UHPLC system (VH-A10-A, VH-P10-A, ThermoFisher Scientific) equipped with an Acquity Premier HSS T3 (2.1x150 mm, 1.7um, Waters) column, at 30°C and a flow of 0.3 ml/min on an injection volume of 5 uL was applied. Eluent A consisted of 10 mM ammonium formate in water with 0.1% formic acid, and eluent B consisted of 10 mM ammonium formate in methanol with 0.1% formic acid.  Short chain fatty acid analysis of Acetic acid, Formic acid, Propanoic acid, 2-Methylpropanoic acid, Butanoic acid, 3-Methylbutanoic acid, Pentanoic acid, 4-Methylpentanoic acid, Hexanoic acid, and Heptanoic acid was performed in a targeted manner on a high-polarity column (ZebronTM ZB-FFAP, GC Cap. Column 30 m x 0.25 mm x 0.25 μm) installed in a GC (7890B, Agilent) coupled with a quadrupole MS (5977B MSD, Agilent). SCFAs were injected by 0.5 uL into a 180°C liner, at a split ratio of 1:50 and constant flow of 4 ml/min. A temperature gradient from 80°C to 190°C over 8 minutes (at a rate of 15°C/min), followed by a rapid ramp from 190°C to 260°C (100°C/min) was used to separate SCFAs. Ref:[1] Doneanu CE, Chen W, Mazzeo JR. UPLC/MS Monitoring of Water-Soluble Vitamin Bs in Cell Culture Media in Minutes. Water Appl. Note. 2011Habitual Coffee Intake Shapes the Gut Microbiome and Modifies Host Physiology and Cognition: double-blind, randomised, parallel design.MS-OmicsThorsten Gravertsolventfecesmass spectrometry assayStool sample were extracted using four times the initial sample weight (wt/vol) of MilliQ water, vortexing until a suspension was reached and centrifugation to separate particulate matter. The supernatant was filtered by centrifugation (Pall AcroPrepTM, 0.2 um, 4.000 g, 4°C, 15 min). For reverse phase analysis, sample extracts were diluted eleven times in mobile phase eluent A (10 mM ammonium formate + 0.1% formic acid in ultrapure water) and fortified with stable isotope (deuterium and 13C) labelled standards before analysis.  For GC-MS-based short-chain fatty acid analysis, performed by MS-Omics (Vedbæk, Denmark)[1], stool extract supernatants were acidified with hydrochloric acid (0.5 M) and fortified with deuterium-labelled standards. Ref:[1] https://cmbio.io/contact-usreference compoundHomo sapienssolventhttps://www.ebi.ac.uk/metabolights/MTBLS13401LC-MS metabolomics data processing was performed untargeted using Compound Discoverer 3.3 (Thermo Scientific) and Skyline 22.2 (MacCoss Lab Software) for peak picking and feature grouping. Raw GC-MS data were processed and quantified in Skyline 22.2[1] and the PARADISe software (v2.6)[2] developed by MS-Omics and collaborators. Ref:[1] Adams KJ, Pratt B, Bose N, Dubois LG, St John-Williams L, Perrott KM, Ky K, Kapahi P, Sharma V, MacCoss MJ, Moseley MA, Colton CA, MacLean BX, Schilling B, Thompson JW; Alzheimer’s Disease Metabolomics Consortium. Skyline for Small Molecules: A Unifying Software Package for Quantitative Metabolomics. J Proteome Res. 2020 Apr 3;19(4):1447-1458. doi: 10.1021/acs.jproteome.9b00640. Epub 2020 Mar 26. PMID: 31984744; PMCID: PMC7127945.[2] Lea G. Johnsen, Peter B. Skou, Bekzod Khakimov, Rasmus Bro, Gas chromatography – mass spectrometry data processing made easy, Journal of Chromatography A, Volume 1503, 2017, Pages 57-64, ISSN 0021-9673, https://doi.org/10.1016/j.chroma.2017.04.052.RandomizationVisitCoffee IDtg@msomics.comBiological samples from human adults were collected as part of the study on the day of Visit 2 (V2), Visit 3 (V3) and Visit 4 (V4). In total, four matrices were collected (saliva, blood, urine and stool) of which stool was analysed by metabolomics and described in this submission.  StoolParticipants were asked to collect the first freshly voided stool samples of the day in plastic containers containing an AnaeroGen sachet (Oxoid AGS AnaeroGen Compact, Fischer Scientific, Dublin). Stool samples were refrigerated using ice packs until delivery to the laboratory, where they were aliquoted and stored at −80°C. Stool samples were collected the day of the visits as well as during the extra timepoints during the coffee washout and coffee intervention.Metabolomicsshort-chain fatty acidpooled quality control samplemetabolite profiling assayThermo Scientific Orbitrap Exploris 240unspecifiedGastrointestinal MicrobiomeHomo sapiens7890b gas chromatographyCoffee5977B MSDtargeted metabolitesexperimental sampleThermo Scientific Vanquish UHPLC Systemreference compounduntargeted metabolitessolventfecesshort-chain fatty acidpooled quality control samplemetabolite profiling assayThermo Scientific Orbitrap Exploris 240unspecifiedGastrointestinal MicrobiomeHomo sapiens7890b gas chromatographyCoffee5977B MSDtargeted metabolitesexperimental sampleThermo Scientific Vanquish UHPLC Systemreference compounduntargeted metabolitessolventfecesFor semi-polar metabolite analysis, the Orbitrap Exploris 240 MS (Thermo Scientific) operated with following parameters: full MS scan, a resolution of 60,000, AGC target Standard, maximum injection time mode auto, and a scan range of 65 to 975 m/z. Data-dependent MS/MS (dd-MS²) parameters included a TopN of 5, resolution of 30,000, AGC target of Standard, Auto maximum injection time, isolation window of 0.4 m/z, and stepped collision energy (NCE) of 20, 40, 60. Dynamic exclusion was set to 2.5s after 1 time to prevent repeated fragmentation of the same ion, with an intensity threshold of 1.0e3 for ion selection, and an apex trigger with a trigger window of 30%. Isotope exclusion was enabled to focus on the most abundant isotopes, and lock masses were used to ensure calibration stability throughout the runs. An electrospray ionization interface was used as a source. Analysis was performed in positive and negative ionization mode in switching (alternating) polarity. Short-chain fatty acid analysis was performed in a targeted manner using a quadrupole MS (5977B MSD, Agilent) in SIM mode equipped with EI source and a 1 min solvent delay. The transfer line was heated to 250°C and ion source temperature was set to 230°C.4-HydroxynonenalDambonitolval-argVogliboseCaprolactamN6-METHYLLYSINE1,4,5-Trihydroxy-5-hydroxymethyl-2-methoxycyclohex-1-en-3-oneC4-CarnitineGuaiacolPectolinarigeningamma-Glu-glnTacrineDIMBOAN.pi.-Methyl-L-histidineasn-lysArg-proMethanesulfonic acidMaraniol1-Methyl-2,3,4,9-tetrahydro-1H-beta-carboline-1,3-dicarboxylic acidNS1800000Allyl mercaptanCapryloylglycine4-HydroxybenzaldehydeMono(3-carboxypropyl) phthalateFurfuralPilocarpineOxprenolol12-Ketodeoxycholic acid2-Ammonio-4-{4-[(2S)-2-ammonio-2-carboxylatoethyl]-1H-imidazol-2-yl}butanoateN6-Acetyl-L-lysine5-(5-Methyl-2-furyl)-2,3-dihydro-1H-pyrrolizine5-Hydroxy-7-methoxy-2,2-dimethyl-6-(3-phenylpropanoyl)-3,4-dihydro-2H-chromen-4-yl hydrogen sulfateMolindoneMevalonic acidArginineZinecard4-Methylcatechol5-Hydroxylysine4,4'-Thiobis(butan-2-one)Caffeic acidhis-glncis-3-Hexenyl Pyruvate2-(1-Ethoxyethoxy)propanoic acidIsotretinoinN-Acetylneuraminic acidPantothenic acidMesalamine2,4,6-Trihydroxy-5-[1-(3-hydroxy-1,1,5-trimethyldecahydrocyclopropa[e]inden-5-yl)-3-methylbutyl]isophthalaldehyde4-(1,2-Dihydroxy-2-propanyl)-1-methyl-1,2-cyclohexanediol8-Hydroxyhexadecanedioic acidLeu-ValSaccharinPipemidic acidMetalaxyldimethylthiambuteneEthyl lactateRo 20-1724Glycylvaline5-Methoxytryptaminemelanostatinlys-thr3-Dehydroquinic acid4-[(1Z)-1-{4-[2-(Dimethylamino)ethoxy]phenyl}-2-phenyl-1-buten-1-yl]phenyl hydrogen sulfateN-lauroylglycine(2S)-3-(1H-Imidazol-4-yl)-2-({[(3S,4S,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]methyl}amino)propanoic acid (non-preferred name)MC05553003-Hydroxy-3-[(3-methylbutanoyl)oxy]-4-(trimethylammonio)butanoateOrnithine3-Methyladenine3-(2-Deoxy-beta-D-erythro-pentofuranosyl)-4,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one5-(N,N-Dimethylcarbamimidamido)-2-oxopentanoic acidSerineβ-PineneL(-)-Carnitine5-[(3aR,4R,6aS)-2-Oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamide3,7-Dimethyluric acid(−)-nabiloneBICglu-proNorpseudopelletierineUric acidMexiletineMFCD000372152-Hydroxycinnamic acidPiceidButabarbitalEupatilinMHPG6-(1-Hydroxyethyl)-3-(hydroxymethyl)-2,7-dioxabicyclo[4.1.0]hept-3-en-5-one(12-Methyl-7-tetraphenyl)methyl hydrogen sulfateGlycylprolylhydroxyproline5-[(1R)-1-(2-Furyl)-3-(methylamino)propoxy]-2-methoxy-1-naphthyl hydrogen sulfateMelatoninDihydroxy Analogue of Mycophenolic Acid(-)-secoisolariciresinolValylvalineN(2)-succinyl-L-ornithine6-Hydroxy-2-(2-hydroxy-2-propanyl)-9-methyl-3,9-dihydrofuro[2,3-b]quinolin-4(2H)-oneMethylsuccinic acidTetradecanedioic acidTraumatic acidOxepanoneEcgonine2-Acetamidohexanedioic acid2,9-Dimethyl-2,9-diazatricyclo[10.2.2.2~5,8~]octadeca-1(14),5,7,12,15,17-hexaene-3,10-diolThreonineTetraacetylethylenediamineDehydroepiandrosterone sulfate4-(2,4-Dihydroxyphenyl)-8-[(Z)-2-(2,4-dihydroxyphenyl)vinyl]-10,18-dihydroxy-14-methyl-3,5,15-trioxahexacyclo[12.7.1.0~2,4~.0~2,12~.0~6,11~.0~16,21~]docosa-6,8,10,16,18,20-hexaen-13-oneLysineRetinyl beta-glucuronideIsopelletierinen-Ribosylhistidine11-dehydro Thromboxane B2(Carbamoylamino)(4-hydroxyphenyl)acetic acid4-AcetamidophenolIsoprenalineSuccinic anhydride2-MethylbutyrylglycineN-(3,4,5-Trihydroxybenzoyl)glycine1-(3-Amino-2,3-dideoxypentofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedioneGuaninePyrimidine1-(2,3-Dihydro-1H-pyrrolizin-5-yl)-1,4-pentanedioneButylparabenN-AcetylphenylalanineAcetanilideXanthosine2,4,6-trihydroxybenzophenoneGlycylleucine4-(METHYLNITROSAMINO)-1-(3-PYRIDYL-N-OXIDE)-1-BUTANONE7-MethylguanineMethyl (2R,3S)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylateL-Hexanoylcarnitine1-methylhypoxanthineProcarbazine1,5-Anhydro-1-(2,4,6-trihydroxyphenyl)hexitolZolmitriptanACPCN-AcetylProlineDO07500004-(5,6-Dihydroxy-6-methyl-1-hepten-2-yl)-1-methyl-1,2-cyclohexanediolN,N-Diethyl-4-methyl-1-piperazinecarboxamide 4-oxideLys-ProbutyrinN-Stearoyltyrosinep-coumaroylagmatine(2S)-6-Amino-2-[(E)-(hydroxymethylene)amino]hexanimidic acidN-VanillyloctanamideLeucyltryptophanN-Benzoylaspartic acidCasimiroinCarnitineHydroquinone(2R,3R)-2-(3,4-Dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl 4-hydroxybenzoate3-[(2Z)-1-Oxo-2-buten-2-yl]pentanedioic acidPhenyl D-glucopyranosiduronic acidDibutyl malateChenodeoxycholic acid 3-sulfateAgomelatine3,4-Dimethoxyphenylacetic acidAla-Tyr2,3,4,9-Tetrahydro-1H-β-carboline-3-carboxylic acidCilazaprilÎ²-D-RibofuranosylcreatinePipecolinic acid1,3,5-Trihydroxy-4-methoxy-10-methyl-9(10H)-acridinoneb-Ala-LysGlycylglutamineAAMU3-[4-methyl-1-(2-methylpropanoyl)-3-oxocyclohexyl]butanoic acid1,3-Dihydroxy-2-propanyl (7Z,10Z,13Z,16Z,19Z)-7,10,13,16,19-docosapentaenoateGramineThymine7-(2,3-Dihydroxy-3-methylbutoxy)-8-(3-methyl-2-oxobutyl)-2H-chromen-2-one1-Methyladenosine(2E)-N-[2-(Dihydroxymethyl)-4-hydroxy-5-methoxyphenyl]-3-(4-hydroxy-3-methoxyphenyl)acrylamideMesalazineETHYL 4-(ACETYLTHIO)BUTYRATETaurinePerindoprilatZalcitabineDH3078000(2R)-1-{[(2-Aminoethoxy)(hydroxy)phosphoryl]oxy}-3-hydroxy-2-propanyl (6Z,9Z,12Z,15Z)-6,9,12,15-octadecatetraenoate4-(2-Aminopropoxy)-3,5-dimethylphenolPirbuterolHexamethylene bisacetamideN-{3-Carboxy-3-[(3-carboxy-3-hydroxypropyl)amino]propyl}homoserineD-Alanyl-D-alanine8-Amino-7-oxononanoic acidAgmatinePyridoxalTrigonelline4-(1-Hydroxy-2-{[6-(4-hydroxy-4-phenylbutoxy)hexyl]amino}ethyl)-2-(hydroxymethyl)phenolN-Nonanoylglycineω-Muricholic acidN-(3,5-Dimethoxybenzoyl)glycine(+)-Thioctic acidN~2~-(Carboxymethyl)arginineButenylcarnitine4-Methoxyaniline13-Isopropyl-3,7,15-trimethyl-14,16-dioxahexacyclo[7.6.1.0~2,13~.0~3,11~.0~4,8~.0~10,15~]hexadecane-1,4,8,9,10,11-hexol3-(4,7-Dimethoxy-1,3-benzodioxol-5-yl)propanoic acidOI1700000(4S)-4-[(2E,4Z)-2,4-Decadienoyloxy]-4-(trimethylammonio)butanoateDL-Nordihydroguaiaretic acid(2E)-3-(3,4-Dimethoxyphenyl)acrylic acid8-Methyl-8-azabicyclo[3.2.1]octane-1,2,3,4,6-pentolN-AcetylglutamineHP1760000carisoprodolQueuosineclotiazepamTetrahydropapaverolineg-Aminobutyryl-lysinethreonylphenylalanineTetrahydro-2-furanylmethyl hydrogen sulfateDopaminePhenylalanineFormiminoglutamic AcidBiotin sulfoneNifedipineMorpholineReduldopamineUracilN-Methyl-Î³-oxo-3-pyridinebutanamideacetyltaurineAgaritineCrotonic acidTryptamineN(1),N(8)-bis(coumaroyl)spermidine2-(2-Amino-2-carboxyethyl)-5-oxotetrahydro-2-furancarboxylic acidpimozideCreatineMinoxidilN-Acetyl-5-oxo-L-norvalinenorhamanN-(3-acetamidopropyl)pyrrolidin-2-oneLysylvaline3,4-Dihydroxyphenylpropionic acid4-[(1E)-3-Methoxy-1-propen-1-yl]phenyl hexopyranosideOctyl gallateEthosuximideHomoanserine3-Succinoylpyridine3-CarboxyindoleSpermic acid9-Hydroxy benzopyreneAdipic acidporphobilinogenNX4900000EnterolactoneAcrylic acid(2Z)-(2,6-Dihydroxy-3,4-dimethoxycyclohexylidene)acetonitrileNaphthalen-2-amineHomocarnosineOlmesartan(+)-yohimbineIsoleucineMethyl 1-hydroxy-7-(hydroxymethyl)-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylateThreonic acidN-{3-[(4-Acetamidobutyl)amino]propyl}acetamide3,4-DimethoxyphenethylamineN~1~-Isopropyl-2-methylpropan-1,2-diamindopaquinone(betaS)-beta,3-Dihydroxy-D-tyrosinearomadendrinO-succinylcarnitinetolnaftateNorepinephrine2'-Deoxysepiapterin3-Benzyl-6-isobutyl-2,5-piperazinedioneL-(+)-Citrulline3-Hydroxy-5-({2-hydroxy-5-oxo-6-[(5,5,8a-trimethyl-2-methylenedecahydro-1-naphthalenyl)methyl]-7-oxabicyclo[4.1.0]hept-3-en-3-yl}methoxy)-3-methyl-5-oxopentanoic acid(+/-)-Camphoric acidmethylguanidinePrenisteine3-Acetamido-2,3,4,4a,9,9a-hexahydro-1H-carbazole-6-carboxamideophthalmic acidγ-Aminobutyric acidSularclavulanic acidHistidine4-IodoanisoleMethyl 2,3-dihydro-3-hydroxy-2-oxo-1H-indole-3-acetate1-[(4E)-4-(4-Methyl-5-oxo-2(5H)-furanylidene)butyl]-2-pyrrolidinone2-Methoxy-phloroglucinolTyraminePhosphoric acidHydroxycarteololPropionic acidSedanolideDeanolOseltamivir4',5,7-TRIMETHOXYFLAVONEIndole-3-carboxyaldehyde3-Mercaptopropionic acidON1225000D-glucosamine-6-phosphate1-{3-Carboxy-3-[(3-carboxy-3-hydroxypropyl)amino]propyl}-2-azetidinecarboxylic acid(5R,6Z,8E,10E,12S,14Z)-5,12,20,20,20-Pentahydroxy-6,8,10,14-icosatetraenoic acidMonocrotophosModavigil(R)Hexanoic acidVanillic acid-4-O-glucuronideTranexamic acidKynurenineN-(4-Amino-1-carboxybutyl)glutamic acid1H-Pyrazol-4-ylmethanol6-Hydroxypentadecanedioic acidLeucylasparagine(4-Ethoxyphenyl)ureaAlanineN-AcetylhistidineTryptophan3-Methoxy-4-hydroxyhippuric acidXanthineβ-Muricholic acidTocainideIsocarboxazid5-Methoxy-3-indoleaceate5-guanidino-2-oxopentanoic acidHis-LeuCholineAsparagine5-Allyl-5-sec-butyl-1,3-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrioneDiacetin4-(Nitrosoamino)-1-(3-pyridinyl)-1-butanol2-HexenoylcarnitineYWA1Nicotinic acidHis-pro5-Phospho-beta-D-ribosylaminepresqualene diphosphate5,8-Dihydroxy-2-(1-hydroxy-3-methoxy-4-oxocyclohexyl)-3,7-dimethoxy-4H-chromen-4-oneα-L-FucopyranosePhenazoneGluconic acidp-coumaroylputrescineN-Acetyl-D-lactosamineheptabarbital1,2,3,4-Tetrahydro-Î²-carboline-3-carboxylic acidN1-Methyl-2-pyridone-5-carboxamideIndoleacetylaspartateTOLMETIN2(1H)-Quinolinone, 4-methoxy-1-methyl-3-(3-methyl-1,3-butadienyl)-, (E)-UP07837002-Hydroxybutyric acid/ 3-Hydroxybutyric acidHydroxyhexanoycarnitineIndole-3-butyric acidMethylol DimethylhydantoinN-trans-FeruloyloctopamineProcaineGalacturonic acid2'-Deoxyadenosinehistidinolepsilon-(gamma-Glutamyl)-lysineMFCD09953737Leucinep-CresolN-[(2S)-2-Hydroxypropanoyl]-L-tryptophanAdenylthiomethylpentosePiperidineS(6)-acetyldihydrolipoamideGlucoheptonic Acidp-Coumaric acidMFCD23380830SulfurolIP3Cyclohexanecarboxylic acidDiethylpyrocarbonateIN001501,7-DimethylxanthineMethohexitalTetrahydroharmolAminohippuric acid2-Amino-3-(1H-imidazol-4-yl)propanal(6Z,10Z)-6,10-Dimethyl-3-methylene-3a,4,5,8,9,11a-hexahydrocyclodeca[b]furan-2(3H)-one8-METHOXYKYNURENIC ACID5,7-DIHYDROXY-3',4',5'-TRIMETHOXYFLAVANONE3,3-Dimethylglutaric acid2-Acetyl-5-hydroxy-3-methoxyphenyl hexopyranoside6,7-DihydroxycoumarinUrolithin BAspartameDeoxyinosineSetoclavineN1,N12-DiacetylspermineN-DesmethyltramadolPentosetyr-thracebutololN-AcetylvalineHexanoylglycinephe-glnVal-Trp1-Isothiocyanato-7-(methylthio)heptaneArecoline15-Keto-PGE2NP-020190pentobarbital2-Amino-5-[2-(4-formylphenyl)hydrazino]-5-oxopentanoic acid3,4-dihydroxyphenylpyruvic acidMFCD00027318Phenylethyl alcoholLeu-arg(S)-?-glycerophosphorylethanolamine(-)-Oxycodone2-Methoxy-2-methyldihydro-3(2H)-thiophenoneGlucosamineDL-Mevalonic acidgamma-Glutamyl-N~5~-acetylornithinetert-Butyl 3-amino-1-methyl-2,3-dioxopropylcarbamateGlycinedihydroxybenzylamine2,4-Dihydroxy-7,8-dimethoxy-1,4-benzoxazin-3-oneN-(Carboxymethyl)norleucine11-beta-Hydroxyandrosterone-3-glucuronide2-Isopropyl-4,6-dimethyl-1,3,5-dithiazinane1,5-Dihydroxy-3,4-dimethoxy-10-methyl-9(10H)-acridinoneN-Acetylglutamic acidAsp-lysMiglitolNL5993600N-AcetylvanilalaninelinatinehexobarbitalMFCD18695608Mycophenolate mofetilpro-gln4-Pyridoxic acid4-pyridoxic acidSinapyl alcoholhercynine1,3,7-Trimethyluric acidfelbamate2-(Carboxyacetamido)benzoic acid2,6,10,10-Tetramethyl-1-oxaspiro[4.5]dec-6-yl acetate3-MethylxanthineO-Ethyl (4-hydroxyphenyl)carbamothioateSalbutamolGlyceric acidNarceine2-methylcitric acid1-(4-Amino-4-carboxybutanoyl)-2-piperidinecarboxylic acidMFCD00153469MidodrineMEGX4-(9H-beta-Carbolin-1-yl)-1,2,4-butanetriol2-Methoxy-3-methylcarbazoleferuloylagmatineUridine9-Methyluric acidPindololHIAAProlineIndole-3-acryloylglycine2-[4-(3-Hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediolMFCD00142316MarimastatAcetylmuramic acidAspartic acidIsoniazid1-(2-Hydroxy-4,6-dimethoxyphenyl)-3-(4-methoxyphenyl)-1-propanoneThiamineGlucuronic acidDolasetronIndole-3-acetic acidMethcathinoneSL4506000NSC 927785-Nitro-2-propoxyaniline1-Methyl-1,2,3,4-tetrahydro-Î²-carboline-3-carboxylic acid5-Indololubiquinol 10Fumaric acidAcetylcarnitine4-Hydroxy-2,5-dimethyl-3(2H)-furanoneleu-gln3,4,13-Trimethyl-5-{[(2Z)-3-(methylsulfanyl)-2-propenoyl]oxy}-12-oxo-11,14-dioxatetracyclo[8.3.1.0~1,10~.0~3,8~]tetradec-2-yl (2E)-2-methyl-2-butenoateTrichothec-9-en-8-one, 4,15-bis(acetyloxy)-12,13-epoxy-3-hydroxy-, (3Î±,4Î²)-Gingerenone C2-(Hydroxymethyl)-1-methyl-3,4,5-piperidinetriol3-hydroxy-3-methyloxindoleN-(2-Methoxybenzoyl)glycine(R)-3-hydroxybutyrylcarnitineGlycylprolinethyronineGly-DL-Phe1-(beta-D-ribofuranosyl)thymine2-Hydroxyfelbamate4-Hydroxy-5-methylfuran-3(2H)-one2,5-DihydroxybenzaldehydeHarmalol5-Amino-6-(4-hydroxybutanoyl)-2,2-dimethyl-2,3-dihydro-4H-chromen-4-oneS-PropylcysteineEthylmalonic acid/ Glutaric acid2-Acetamido-2-deoxy-3-O-(6-deoxy-alpha-L-galactopyranosyl)-D-glucoseSpectinomycin(-)-Shikimic acidUrocanic acidPropionylcarnitineHexose dimermeprobamateN~6~,N~6~-Dimethyllysine4-Aminobenzoic acidTDP-2Flavokawain ALeucyltyrosineclocinizine(2E)-3-(4-Hydroxy-3-methoxyphenyl)-N-(4-oxobutyl)acrylamideArg-GlyhypaphorineZearalenone5-MethylcytidinePiperineCyclohexanonePrunasinRivastigmineIndomethacin Related Compound AAcetophenone6-Acetamido-2-oxohexanoic acid4-[(2E,4Z)-6-Carboxy-2,4-heptadien-2-yl]-3-(carboxymethyl)prolineAcetylcadaverineCreatinine2-O-alpha-L-fucopyranosyl- GalactoseFB9500000PyridoxinePimelic acidL-(+)-Erythrulose4-Hydroxy-3-methoxymandelic acidCyclamic acidMethyl (2Z,3E,5Z,7E,9E)-2-ethylidene-11-[4-hydroxy-4-(2-hydroxyethyl)-2-oxo-6-oxa-3-azabicyclo[3.1.0]hex-1-yl]-4,6,10-trimethyl-11-oxo-3,5,7,9-undecatetraenoateValinesaccharopineStachydrinemiglustatButyl isothiocyanateCoixol5,4'-dihydroxy-3,3'-dimethoxy-6,7-methylenedioxyflavoneMFCD08063737diethylcarbamazineAF4878000HistidylglycineR-(+)-Etiracetam2-Hydroxy-4-(methylthio)butanoic acidbutalbitalN~6~-[5-(1,2-Dithiolan-3-yl)pentanoyl]-D-lysineTiglic acidTheobrominePregabalin1-(beta-D-Ribofuranosyl)-1,4-dihydronicotinamideItaconic acidLeu-LeuBetaine7-Sulfocholic acidCoprineButylphthalideJasmonic acidArabic acid(+/-)-HesperetinalliinAtenololCytidine2-Acetyl-6-hydroxy-7-(hydroxymethyl)-1,5,6,7-tetrahydro-4H-azepin-4-one6-Methylhept-5-en-2-onetyr-gln2-Aminoadipic acidProcaterolSECONALGly-LysTO01279002-Isobutyl-3-methoxypyrazineasn-val3-Acetamido-8-hydroxy-2,3,4,4a,9,9a-hexahydro-1H-carbazole-6-carboxamide2-(Acetoxymethyl)-4-(2-amino-6-oxo-3,6-dihydro-9H-purin-9-yl)butyl acetate2,3-Dihydroxypropyl 3,4,5-trihydroxybenzoateGuanadrelTetrahydrofolic acidN-Methylaspartic acidMetoprolol3-hydroxyoctanoylcarnitine3-Hydroxy-3-(2,3,4-trimethoxyphenyl)propanoic acidHyodeoxycholic acidNudifloramideARECOLINEN-[4-(5-Amino-2,2-dimethyl-4-oxo-3,4-dihydro-2H-chromen-6-yl)-1-hydroxy-4-oxo-2-butanyl]formamide3-(6-Hydroxy-7-methoxy-1,3-benzodioxol-5-yl)propanoic acidAPMIsonicotinic acidoxamniquineO-propenoyl-D-carnitine8-hydroxy-7-methylguanine7-Aminomethyl-7-deazaguanineSucraloseN2-AcetyllysineN-(1-Methyl-4-oxo-4,5-dihydro-1H-imidazol-2-yl)alanine(E)-3,4,5-Trimethoxycinnamic acidtranexamic acid2-(3,4-Dimethoxyphenyl)-5,7,8-trihydroxy-3-methoxy-2,3-dihydro-4H-chromen-4-one4-Guanidinobutyric acidL-Saccharopine2-Hydroxy-3,4,5-trimethoxybenzoic acidarg-alaTaxifolinKynurenic acidN-AcetylprocainamideLisinoprilCiclopiroxN-[2-(3,4-Dihydroxyphenyl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)propanamide4-Hydroxy-3-nitrophenylacetic acidTyrosolbeta-D-Ethyl glucuronide(3S)-3-{[(2E)-3-Carboxy-2-propenoyl]oxy}-4-(trimethylammonio)butanoateN-(2,3,4-Trimethoxybenzoyl)glycine1-[(3-Carboxypropyl)amino]-1-deoxy-beta-D-fructofuranoseezetimibeD-α-Hydroxyglutaric acidcarbinoxamine6-Myoporol(2E)-3-Methyl-4-(sulfooxy)-2-butenoic acidIndole-3-carbidolasn-proL-HistidinolGabapentin2-(1,3-Benzodioxol-5-yl)-5,7-dimethoxy-3-chromanolGENTISEINCarnosineN-Acetylarginine5-Amino-6-(3-hydroxy-4-methoxybutanoyl)-2,2-dimethyl-2,3-dihydro-4H-chromen-4-oneO,N-DIDESMETHYLTRAMADOLleucolinelys-leu2-Acetyl-1-pyrroline14-Hydroxy-3,9-dimethyl-12-methylene-5,8,10-trioxatetracyclo[9.3.1.0~1,9~.0~2,7~]pentadecane-6,13-dione3-Methylcrotonylglycine(2R,3S)-3-Hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acidDIACETIN MONOPROPANOATEPsilocinSerotoninDeoxyuridineentecavir3,4,15-Trihydroxy-12,13-epoxytrichothec-9-en-8-yl 3-methylbutanoateAsparaginyl-4-hydroxyproline7-ketodeoxycholic acidFerulic acid6,11-Dihydroxy-2,2-dimethylpyrano[3,2-c]xanthen-7(2H)-oneN-(4-Aminobutyl)-N-(3-aminopropyl)hexanamideFlutamideglutethimideLeucylproline2-Amino-2-deoxy-4-O-Î²-D-galactopyranosyl-D-glucoseALA-PROIndole-3-propionic acidN-AcetylmannosamineGlu-Glu1,7-Dimethyluric acidHexoseMFCD000204241-(4-Aminobutyl)ureaAprobarbitalMimosineserine phosphoethanolamine dizwitterion2-HydroxyphenylalaninemethocarbamolDL-CitrullineHomovanilic acidTyrosine1,3,6-Trihydroxy-5-methoxyxanthoneDL-Carnitine3-(3-Hydroxyphenyl)propanoic acidHomoarginineCoumarin1-pyrrolineLys-pheSuccinic acidTemozolomide3-HydroxymonoethylglycinexylidideGly-TrpLinamarinlys-tyrHippuric acidFormylkynurenine3-Aminosalicylic acid(4E)-2-Amino-3-oxo-4-undecenoic acidN8-AcetylspermidineArenaineN,N-DimethylanilineYV8195000N6,N6,N6-Trimethyl-L-lysine5-MethyluridineHomocitrullineNicotinuric acidIsobutyric acid2-C-Methyl-erythritol-4-phosphoric acidKYNURAMINE1,2-Dihydro[1,3]thiazolo[2',3':2,3]pyrimido[4,5-b]indole-1-carboxylic acid6-hydroxypseudooxynicotine1,1'-[1,12-Dodecanediylbis(oxy)]dibenzene(4beta,8alpha,9R)-6'-Methoxycinchonan-3,9-diolL-gamma-Glutamyl-L-leucineL-gamma-Glutamyl-L-valineMethylimidazoleacetic acid3-(2,3-Dihydroxy-3-methylbutyl)-4-methoxy-1-methyl-2(1H)-quinolinonePanthenolCholic acidL-(+)-ERGOTHIONEINE1-(4-Hydroxy-3,5-dimethoxyphenyl)-1,2,3-propanetriol(-)-Oxymorphone3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acidprocainamideN-(4-Hydroxy-3,5-dimethoxybenzoyl)glycine(3S)-3-{[(2E)-4-Carboxy-2-butenoyl]oxy}-4-(trimethylammonio)butanoate(S)-2-hydrazino-3-(4-hydroxy-3-methoxyphenyl)-2-methylpropionic acid5-acetamido-6-formamido-3-methyluracil3-[(3-Methylbutyl)nitrosoamino]-2-butanone3-MethylhistidineAla-GlnCaffeineArsenobetaineGalactosamine4-HydroxyprolylleucineFusarochromanonespectinomycinHydroxypropionylcarnitine7alpha-Hydroxy-3-oxochol-4-en-24-oic acidMFCD02728197Sebacic acidYU0650000DihydrouracilNL8513000N-Acetylhistamine(8)-GingerolTetramethylpyrazineTheophyllinePyrophosphoric Acidg-ButyrobetaineN-AcetylornithineGulonic acid γ-lactoneHeliettintrans-4-Carboxymethylenebut-2-en-4-olideCystathionine ketimine3,4-MethylenedioxyamphetamineN-LACTOYL ETHANOLAMINE PHOSPHATEDodecanedioic acidYQ1927500Aspartyl-L-prolinemesifuraneS-AdenosylmethioninePentosidineHypusineQuinic acidMefenamic acidVorinostat2,4-Dihydroxybenzoic acidAcetylcholinen-Propyl GalIate4-(METHYLNITROSAMINO)-1-(3-PYRIDYL-N-OXIDE)-1-BUTANOLMFCD00025555Kahweofuranshrimp shellThymidineUrsodeoxycholic acidS-AllylcysteineOrotic acidVal-ServalganciclovirMalic acidCotinineLeucylalanineAllyl Methyl SulfideDL-StachydrineHistamineN-AcetyltyrosineO-heptanoylcarnitineTraumatinYangonin(4R,5S,9S,10R,12S,13S)-1,5,9-Trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadecan-10-olthr-trp2,5-Dimethyl-4-ethoxy-3(2H)-furanoneMethionine sulfoxideMethyl thiobutyratetyramine sulfateSeryltyrosineAzelaic acidValyl-4-hydroxyprolinePyrrolidine1-(4-Hydroxy-3-methoxyphenyl)-3,5-diacetoxyoctane3-(3-Hydroxyphenyl)-2-(4-hydroxyphenyl)-4-[(E)-2-(4-hydroxyphenyl)vinyl]-2,3-dihydro-1-benzofuran-6-ol(DL)-3-O-MethyldopaEpinephrine2,5-Dihydroxybenzoic acid/ 3,4-Dihydroxybenzoic acidN-Acetyl-L-leucineN~6~-OctanoyllysineDeoxyadenosine monophosphate3,4-Dihydroxyphenylglycol(+)-S,S-EthambutolD-(-)-Morphine(3S,4S)-7,12-Dimethyl-3,4-dihydro-3,4-tetraphenediolDeoxycholic acid3b-Hydroxy-5-cholenoic acidDL-AtenololValylproline3-PHENYLPROPYL CINNAMATE(+/-)-Metanephrine3-[(1R,2R)-2-(Aminomethyl)-1-hydroxycyclohexyl]phenolDinoseb4-[(E)-2-(3,4,5-Trimethoxyphenyl)vinyl]phenolfalseHabitual Coffee Intake Shapes the Gut Microbiome and Modifies Host Physiology and Cognition: double-blind, randomised, parallel designCoffee influences multiple physiological processes, including gut function, stress, cognition, and the microbiome. However, the mechanisms underlying these effects remain poorly understood. In this study, we examined coffee’s impact on the microbiota–gut–brain axis—a bidirectional communication pathway between the gut microbiome and the brain—and assessed whether these effects occur independently of caffeine in healthy participants. Our primary outcome was microbiota composition and function, whereas the secondary outcome was gut microbial metabolites and coffee-related metabolites (NCT05927038 and NCT05927103). Significant group differences emerged in faecal microbiome composition, with coffee drinkers showing increased relative abundance of Cryptobacterium and Eggerthella species, alongside reduced levels of the metabolite’s indole-3-propionic acid, indole-3-carboxyaldehyde, and the neurotransmitter γ-aminobutyric acid. Behaviourally, coffee drinkers exhibited greater impulsivity and emotional reactivity, whereas non-coffee drinkers demonstrated better memory performance. Some alterations in the faecal metabolome were reversible following coffee abstinence, and reintroduction triggered acute microbiome changes independent of caffeine. An integrated model identified nine key metabolites—including theophylline, caffeine, and selected phenolic acids—strongly linked to microbial species and cognitive measures. These findings reveal previously unrecognised effects of coffee on the microbiota–gut–brain axis, suggesting that microbiome profiles could potentially predict coffee consumption patterns and highlighting a close association between coffee intake and gut microbial composition.2026-03-262025-11-27MTBLS13401HMDB:HMDB0001185HMDB:HMDB0000301HMDB:HMDB0304061HMDB:HMDB0304171HMDB:HMDB0341150HMDB:HMDB0041901HMDB:HMDB0000733HMDB:HMDB0004193HMDB:HMDB0031554HMDB: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:16135CHEBI:28484CHEBI:74903CHEBI:15366CHEBI:30772CHEBI:45571CHEBI:30776CHEBI:17418CHEBI:30768CHEBI:27596CHEBI:15728CHEBI:15355CHEBI:16467CHEBI:17196CHEBI:16347CHEBI:15354CHEBI:28834CHEBI:73922CHEBI:17992CHEBI:15971CHEBI:17191CHEBI:27911CHEBI:16437CHEBI:63154CHEBI:16543CHEBI:31882CHEBI:15729CHEBI:46905CHEBI:17115CHEBI:15741CHEBI:76308CHEBI:28946CHEBI:18385CHEBI:16857CHEBI:545687CHEBI:18123CHEBI:16828CHEBI:17895CHEBI:17568CHEBI:18107CHEBI:25858CHEBI:16020CHEBI:17189CHEBI:37023CHEBI:50613CHEBI:86366CHEBI:1427CHEBI:86655CHEBI:62207CHEBI:46195CHEBI:76247CHEBI:1127735CHEBI:17597CHEBI:17405CHEBI:18040CHEBI:45996CHEBI:28664CHEBI:57589CHEBI:21615CHEBI:30832CHEBI:17431CHEBI:16977CHEBI:17053CHEBI:48131CHEBI:41139CHEBI:27732CHEBI:15727CHEBI:16359CHEBI:127762CHEBI:16919CHEBI:16737CHEBI:17562CHEBI:28997CHEBI:16450CHEBI:4676CHEBI:18243CHEBI:28918CHEBI:741548CHEBI:17620CHEBI:18012CHEBI:33198CHEBI:47977CHEBI:42717CHEBI:32398CHEBI:15428CHEBI:73514CHEBI:17587CHEBI:64390CHEBI:37741CHEBI:18089CHEBI:27747CHEBI:85981CHEBI:17443CHEBI:545959CHEBI:16411CHEBI:28238CHEBI:43580CHEBI:6032CHEBI:18344CHEBI:16946CHEBI:15603CHEBI:73527CHEBI:18019CHEBI:30797CHEBI:27376CHEBI:17016CHEBI:35704CHEBI:40521CHEBI:17533CHEBI:21553CHEBI:45744CHEBI:16259CHEBI:21560CHEBI:21563CHEBI:15940CHEBI:18357CHEBI:32374CHEBI:53455CHEBI:17295CHEBI:30531CHEBI:17964CHEBI:28821CHEBI:17203CHEBI:53210CHEBI:17310CHEBI:16709CHEBI:17521CHEBI:41865CHEBI:28790CHEBI:15891CHEBI:28177CHEBI:15908CHEBI:17748CHEBI:17821CHEBI:16765CHEBI:17775CHEBI:16704CHEBI:9907CHEBI:16414CHEBI:17712CHEBI:134216CHEBI:16865CHEBI:81299