MetaboLights

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ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/m_MTBLS12087_LC-MS_negative_reverse-phase_metabolite_profiling-1_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/m_MTBLS12087_LC-MS_positive_reverse-phase_metabolite_profiling-1_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/s_MTBLS12087.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/a_MTBLS12087_LC-MS_positive_reverse-phase_metabolite_profiling-1.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/a_MTBLS12087_LC-MS_negative_reverse-phase_metabolite_profiling-1.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_P3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_C6.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_P1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_QC01.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_C5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_P2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_P10.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_QC04.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_P2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_C4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_P5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_P4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_C8.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_QC03.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_C9.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_P3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_C6.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_P4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_P6.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_C10.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_P5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_C7.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_C8.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_QC02.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_P10.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_C7.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_P6.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_C2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_QC02.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_C3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_P7.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_P7.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_C3.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_C4.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_P8.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_QC04.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_C10.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_C9.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_C5.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_C1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_P1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_QC03.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_P9.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_P8.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_C2.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_P9.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/POS_Ga17JY_C1.rawftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087/FILES/RAW_FILES/NEG_Ga17JY_QC01.rawprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS12087The 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. MetaboLightsPublicLiquid Chromatography MS - negative - reverse phaseLiquid Chromatography MS - positive - reverse phaseThe 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 x 2.1 mm i.d., 1.8 μm; Waters, USA) 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: 0.0-3.0 min, mobile phase B was increased from 0% to 20%; 3.0-4.5 min, mobile phase B was increased from 20% to 35%; 4.5-5.0 min, mobile phase B was increased from 35% to 100%; 5.0-6.3 min, mobile phase B was maintained at 100%; 6.3-6.4 min, mobile phase B was decreased from 100% to 0%; 6.4-8.0 min, mobile phase B was maintained at 0%. Separation gradient in negative ion mode: 0.0-1.5 min, mobile phase B rises from 0 to 5%; 1.5-2.0 min, mobile phase B rises from 5% to 10%; 2.0-4.5 min, mobile phase B rises from 10% to 30%; 4.5-5.0 min, mobile phase B rises from 30% to 100%; 5.0-6.3 min, mobile phase B linearly maintains 100%; 6.3-6.4 min, the mobile phase B decreased from 100% to 0%; 6.4-8.0 min, the mobile phase B was linearly maintained at 0%. The flow rate was 0.40 mL/min and the column temperature was 40 °C.Microbial-derived Hyodeoxycholic Acid Ameliorates Painful Diabetic Neuropathy by Modulating Dorsal Root Ganglion TLR4-Mediated Neuroinflammation Signaling Pathway.Ye JiangPeking university third hospitalblood serummass spectrometry assayBriefly, 100 μL liquid sample was added to a 1.5 mL centrifuge tube with 400 μL solution (acetonitrile:methanol, 1:1, v:v) containing 0.02 mg/mL internal standard (L-2-chlorophenylalanine) to extract metabolites. The samples were mixed by vortex for 30 s and low-temperature sonicated for 30 min (5 °C, 40 KHz). The samples were placed at -20 °C for 30 min to precipitate the proteins. Then the samples were centrifuged for 15 min (4 °C, 13,000 x g). The supernatant was removed and blown dry under nitrogen. The sample was then re-solubilized with 100 µL solution (acetonitrile:water, 1:1) and extracted by low-temperature ultrasonication for 5 min (5 °C, 40 KHz), followed by centrifugation at 13,000 x g and 4 °C for 10 min. The supernatant was transferred to sample vials for LC-MS/MS analysis.Rattus norvegicushttps://www.ebi.ac.uk/metabolights/MTBLS12087Yongzheng Han. hanyongzheng@bjmu.edu.cn.Yanhan Lyu. lvyanhanor@126.com.Zixian Zhang. zixianzhang0118@163.com.Ye Jiang. Peking University Third Hospital. 49 North Garden Rd., Haidian District, Beijing, China. jyeaho@163.com. 8.61821E+12.Guo-gang Xing. Peking University. ggxing@bjmu.edu.cn.Dongshen Yang. 2211210467@stu.pku.edu.cn.Min Wei. Peking University Third Hospital. 49 North Garden Rd., Haidian District, Beijing, China. weimin@bjmu.edu.cn.Qian Chen. qian.chen@zju.edu.cn.Min Li. Peking University Third Hospital. liminanesth@bjmu.edu.cn.Jiayin Shou. 1910301106@pku.edu.cn.Shixiong Shen. shixiong_shen@hsc.pku.edu.cn.Zhuoying Yu. zhuoyingyu@bjmu.edu.cn.Jie Cai. caij1212@163.com.Daqing Ma. Children’s Hospital, School of Medicine, Zhejiang University. d.ma@imperial.ac.uk.Jing Yang. Peking University Third Hospital. 49 North Garden Rd.,Haidian District Beijing 100191,P.R.China. yangjing@pku.edu.cn.The pretreatment of LC-MS raw data was performed by Progenesis QI (Waters Corporation, Milford, USA) software, and a 3D data matrix in CSV format was exported. The information in this 3D 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.RF treatmentBiological replicatejyeaho@163.comRats were euthanized, and blood was collected for serum extraction.Metabolomicsultra-performance liquid chromatography-mass spectrometrypooled quality control sampleuntargeted analysisThermo Scientific Q Exactive HF-XRattus norvegicusblood serumuntargeted metabolitesThermo Scientific Vanquish Horizon UHPLC SystemDiabetic NeuropathiesIntestinal Floraexperimental sampleultra-performance liquid chromatography-mass spectrometrypooled quality control sampleuntargeted analysisThermo Scientific Q Exactive HF-XRattus norvegicusblood serumuntargeted metabolitesThermo Scientific Vanquish Horizon UHPLC SystemDiabetic NeuropathiesIntestinal Floraexperimental sampleThe 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 °C; sheath gas flow rate at 50 arb; Aux gas flow rate at 13 arb; ion-spray voltage floating (ISVF) at -3500 V in negative mode and 3500 V in positive mode, respectively; Normalized collision energy, 20-40-60 V rolling for MS/MS. Full MS resolution was 60000, and MS/MS resolution was 7500. Data acquisition was performed with the Data Dependent Acquisition (DDA) mode. The detection was carried out over a mass range of 70-1050 m/z.Soyasapogenol B 3-O-b-D-glucuronide(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(6-imino-1-methylpurin-9-yl)oxolane-3,4-diolAlpha-CEHC glucuronideP-CHLOROPHENYLALANINEXestoaminol C13(S)-HOTrE5-AminopentanamideSuccinoadenosineN1,N12-DiacetylspermineN-di-Demethyl roxithromycinCaffeic AcidIndolylacryloylglycineCumene11-bromo-undecanoic acid2-Pyridylacetic acidL-gamma-glutamyl-L-valine6-[5]-ladderane-1-hexanol1-KestosePhenylalanylprolineArginyl-LeucineHyocholic acidHercynine6-[1-carboxy-2-(4-methoxy-1-benzofuran-5-yl)-2-oxoethyl]-3,4,5-trihydroxyoxane-2-carboxylic acidN1-AcetylspermidinePGF2a ethanolamide20,24-Epoxy-25,26-dihydroxydammaran-3-one5-Hydroxyindoleacetic acidGingerglycolipid BGingerglycolipid CGlyceryl 5-hydroxydecanoate3,3'-Dihydroxy-4',5,7-trimethoxyflavanKinetensin 4-7(+/-)7-epi Jasmonic AcidImidazole lactateFuraneol 4-(6-malonylglucoside)Jasmone3-Methoxytyrosine15d PGD2{[1-(4-methoxyphenyl)pentan-3-yl]oxy}sulfonic acidStearoylethanolamide3,4-DimethylstyreneEstriolD-erythro-Sphingosine C-17Tetraphyllin BD-erythro-Sphingosine C-15Valyl-LysineL-phenylalanyl-L-prolineN2-Succinyl-L-glutamic acid 5-semialdehydeTrans-4-Coumaric acidHydroxysafflor yellow A3,3',4',7-TetrahydroxyflavoneN-AcetylcadaverineLysoPE(0:0/18:2(9Z,12Z))Temazepam4-Methyl-5-thiazoleethanolLysoPE(16:1(9Z)/0:0)Oleamide6-({4,5-dihydroxy-2-[hydroxy({2,3,4-trihydroxy-6-oxo-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]cyclohexa-1,4-dien-1-yl})methyl]oxan-3-yl}oxy)-3,4,5-trihydroxyoxane-2-carboxylic acid3-Hydroxydodecanedioic acidPE(16:0/0:0)Kainic acidDehydrocarpaine IN-Nitrosoguvacoline4-Pyridoxic acid3,4,2',4',6'-PentahydroxychalconeButoctamide hydrogen succinateN-Succinyl-L-glutamateRibothymidine(-)-Glycinol6-[(E)-2-(2H-1,3-benzodioxol-5-yl)ethenyl]-5-hydroxy-4-methoxy-5,6-dihydro-2H-pyran-2-oneumbelliferoneTyrosyl-Aspartate3-Oxocholic acidLysoPC(18:1(11Z))2-FormaminobenzoylacetateNeuromedin B (1-3)DioscoretineProlylphenylalanineSoyasaponin IVCotinine glucuronideMethyl beta-D-glucopyranosideHomoveratric acidAminoadipic acidPorsonHydroxyprolyl-Leucine2-Indolecarboxylic acid(2S)-2-{[1-(R)-Carboxyethyl]amino}pentanoateethoxyquin3-(4-hydroxyphenyl)acrylic acid2'-Apo-beta-carotenalC12:4n-2,4,8,101H-Indol-3-ylacetyl-myo-inositolGlutaminylhydroxyprolineL-Thyronine1-Methylguanine(R)-SerineMeta-O-Dealkylated flecainideGlutamylprolineC16 SphingosineIsopropyl hexadecanoate3a,7b,21-Trihydroxy-5b-cholanoic acidValyl-Tyrosine4-Hydroxyproline galactosideGlaudine6-Hydroxyindolelactate4-PIOLLysoPC(20:3(5Z,8Z,11Z))5-Methyl-2-furaldehydeL-HisidineGamma-GlutamylisoleucineMethyl-delta-iononeCysteinyl-GlutaminePalmitoleamide26-Glucosyl-1,3,11,22-tetrahydroxyergosta-5,24-dien-26-oate(-)-Epinephrine9-OxoODEN-Acetyl-L-glutamic acidIsovalerylglutamic acid4-Isopropylbenzoic acidKetoisophoroneAsterosterol3-O-Acetylepisamarcandin3-Pyridinebutanoic acid2-Hydroxycinnamic acidcresopyrine6b-Hydroxy-8a-methoxy-7(11)-eremophilen-12,8-olide2-Hydroxy-6-oxo-6-phenylhexa-2,4-dienoateTyrosyl-ProlineIsopentenyl adenosine3,7-Dimethyl-8,11-dioxo-2E,6E,9E-dodecatrienalAlpha-Methylstyrene3-Hydroxycinnamic acidPinolenic AcidHumulolGlycylprolineKudzusaponin SA2Kudzusaponin SA1LysoPE(20:4(5Z,8Z,11Z,14Z)/0:0)N-(3-Aminopropyl)morpholineMusabalbisiane C2-(4-Methoxyphenyl)acetic acid3-hydroxyundecanoyl carnitineUrocanic acid20-trifluoro-LTB4Oblongolide2-MethylindolineN-acetyl-4-aminosalicylic acidC1'-C9-Glycosylated UWM68-(1,2-dihydroxypropan-2-yl)-2-oxo-2H,8H,9H-furo[2,3-h]chromen-9-yl 3-methylbut-2-enoatePhenylacetaldehydeAsperageninN-AcetylglucosamineCurcumenol(4R,6S)-p-Menth-1-ene-4,6-diol 4-glucosidecitropten2-IndanoneLysoPC(16:1(9Z)/0:0)N-Acetyl-4-O-acetylneuraminic acidHovenine ASerratol2-Phenylethyl octanoateOctadecanamide1-LinoleoylglycerophosphocholineHerculin2-Ethylacrylic acidCavinineD-PantethinePimelic acidMetabolite M6Yucalexin P17N,N'-bis(3-aminopropyl)butane-1,4-diamine3-Formyl-6-hydroxyindoleHistidinalSuccinylmonocholinePalmitic amideDG(18:4(6Z,9Z,12Z,15Z)/18:3(6Z,9Z,12Z)/0:0)2-Amino-3-carboxymuconic acid semialdehyde10,20-Dihydroxyeicosanoic acidGlutaminyl-Hydroxyproline5-MethoxytryptophanYucalexin P15L-UrobilinogenCarboxyprimaquine6-LactoyltetrahydropterinIndole-3-carboxaldehydeStearic acid4-(aminomethyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol7,8-Dihydro-3b,6a-dihydroxy-alpha-ionol 9-[apiosyl-(1->6)-glucoside]Jasmonic acidGamma-Glutamyl-S-methylcysteine sulfoxideAlpha-Aspartyl-lysineC14:5n-1,3,5,7,9PisumionosideDiscadenineL-Methionine S-oxideLysoPC(18:0)AphidicolinN2-Malonyl-D-tryptophanTaurochenodeoxycholic acidDiacetyldideisovaleryl-RhodomyrtoxinTrimethylamine N-oxideIsoleucyl-Hydroxyproline2-[2,4,6-trihydroxy-3-(3-methylbut-2-en-1-yl)phenyl]acetic acidGenipin1,4-Methylimidazoleacetic acid3-ketosphinganine4-oxo-1H-quinoline-2-carboxylic acidPyridine N-oxide glucuronide4-Hydroxy-4-(3-pyridyl)-butanoic acidDeoxydihydro-artemisininMycosporine4-Pyrimidine Methanamine (hydrochloride)KAPAGamma-L-Glutamyl-gamma-L-glutamyl-L-methionine1-Oxo-1H-2-benzopyran-3-carboxaldehydeThymineL(-)-Pipecolinic acid9R,10S-Epoxy-3Z,6Z-eicosadiene4-methoxybenzene-1,3-diolPE(14:0/0:0)7-Ketolithocholic Acid(2'E,4'Z,7'Z,8E)-Colnelenic acidFarnesyl acetoneD-UrobilinogenEthyl 3-hydroxydodecanoate2-FormyloxymethylclavamBeta-IonolIsonicotinic acidCynaratriolGamma-Glutamyl-beta-aminopropiononitrile1-MethylhistamineAcetylshikoninGamma-Glu-Leu24-HydroxycalcitriolPE(P-16:0/14:1(9Z))12-ketolithocholic acid(S)-methopreneTrigoforin(4E,8E,10E-d18:3)sphingosineCamellenodiolCyclododecanoneAdenosine 3'-monophosphateAlpha-Vetivone10-EpijunenolP-Mentha-1,3,5,8-tetraenePalmitoylethanolamide(17alpha,23S)-17,23-Epoxy-29-hydroxy-27-norlanosta-1,8-diene-3,15,24-trioneL-L-Homoglutathione3''-Deamino-3''-oxonicotianamineGibberellin A12Citreoviridin C7,8-dihydroxy-4-methyl-coumarinDopamine glucuronide4-Hydroxy-2,6,6-trimethyl-3-oxo-1,4-cyclohexadiene-1-carboxaldehydeLeucyl-Valine5,7-dihydroxy-2-(4-hydroxyphenyl)-6-methoxy-chromone(3beta,17alpha,23S)-17,23-Epoxy-3,28,29-trihydroxy-27-norlanost-8-en-24-oneCD 1790L-phenylalanyl-L-hydroxyprolineLysyl-Lysine1-MethylguanosineL-Pyridosine(E)-2-Tridecene-4,6,8-triyn-1-olFluprostenol Lactone Diol3,5,5-Trimethyl-3-cyclohexen-1-oneCelastrolCaryophyllene oxideMalvidinFeruloylputrescineWithaperuvin EN-methylisoleucineLysoPC(P-16:0)PA(15:0/22:4(7Z,10Z,13Z,16Z))2-Hydroxy-7,8-dehydrograndifloroneMiraxanthin-VMethyl 2-undecynoateNiacinamideCasticinEupacunolinTrolamineUracilEicosapentaenoic acidMelleolideLagerstroemine(2S)-2-amino-3-[4-hydroxy-3-(sulfooxy)phenyl]-2-methylpropanoic acidCreatine(S)-(-)-Perillyl alcohol16-Hydroxy hexadecanoic acidL-Glutamic AcidHeptadecanoyl EthanolamideHypoglycin BDHAP(10:0)DL-Citrulline2-Amino-4-oxo-4-alpha-hydroxy-6-(erythro-1',2',3'-trihydroxypropyl)-5,6,7,8-tetrahydroxypterinN-heptanoyl-homoserine lactoneCytosineLeridolIndoleacrylic acidFerulic Acid4-[5]-ladderane-butanoic acidNiazimin ARicinoleic Acid methyl esterThreoninyl-Gamma-glutamate(3S,7E,9S)-9-Hydroxy-4,7-megastigmadien-3-one 9-glucosideDinor-PGE2(3b,4b,11b,14b)-11-Ethoxy-3,4-epoxy-14-hydroxy-12-cyathen-15-al 14-xylosideSuccinic acid23-trans-p-Coumaroyloxytormentic acidHippuric acid3'-Amino-3'-deoxythimidine21-DeoxycortisolLysoPC(0:0/18:0)MG(15:0/0:0/0:0)4-Hydroxy-2-quinoloneD-Pipecolic acid(1alpha,3beta,20S,22R,24S,25S)-PubesceninCytarabineHomovanillic acidL-(-)-TyrosineN-Succinyl-L,L-2,6-diaminopimelateHaemanthidine2-Aminobut-2-enoateMethylgingerolOxindoleHexyl glucosideCorchorosol A1-pentadecanoyl-glycero-3-phosphate2-Hydroxyphenethylamine7-Tridecynoic acidEthyltestosterone6-O-Methylguanine(3beta,5alpha,9alpha,14alpha,22E,24R)-3,5,9,14-Tetrahydroxyergosta-7,22-dien-6-oneLumichrome2-PyrrolidinoneAminohydroquinonePC(16:0/0:0)[U]Corchorifatty acid FN-Acetyl-L-phenylalaninePS(O-16:0/0:0)22-Angeloylbarringtogenol CTauro-alpha-muricholic acid4-HydroxymedicarpinM-Coumaric acidAscochitin4-Hydroxycinnamic acidP-Tolualdehyde11-keto Fluprostenol2,5-Dimethylbenzaldehyde9,12,15-Octadecatrien-1-olPERICIAZINEL-phenylalaninol(S)-5-Amino-3-oxohexanoate6E,8E,12E,14E-Hexadecatetraen-10-ynoic acidChalcolactoneSoyasaponin INeryl butyrate5-(2'-Carboxyethyl)-4,6-DihydroxypicolinateCassythineSoyasaponin VN4-Acetylcytidine6-HydroxyetodolacCorchorifatty acid DLucidone C6-O-Acetylaustroinulin10,12-Tetradecadiene-4,6-diynoic acid, (E,E)-4-formyl IndoleAvocadene 4-acetate(R)-3-Hydroxybutyric acid(R)-MandelamideN-AcetyltyramineP-HydroxybenzaldehydeBetaine aldehyde(+/-)-Ibuprofen1-Pyrroline2-Methylguanosine7,12-Dihydroxy-3,11,15,23-tetraoxolanost-8-en-26-oic acidVulgarone A4-AndrostenediolL-Glutamine6,7-dihydro-12-epi-LTB4Lepadin D1-(1,2,3,4,5-Pentahydroxypent-1-yl)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylate(+)-15,16-Dihydroxyoctadecanoic acidFisetin 8-C-glucosideLysoPC(20:4(8Z,11Z,14Z,17Z))Oryzalic acid BN-DecanoylglycineGuaiazuleneDihydrocaffeic acid 3-sulfateAH 6809thymoquinone2,6-Piperidinedicarboxylic acidIndole-3-acetamideBoviquinone 411-Hydroxyeicosatetraenoate glyceryl esterPhenylpropionylglycineLyso-PAF C-1612,13-EpOMEN-Arachidonoyl-3-hydroxy-gamma-Aminobutyric AcidGlabreneSuccinylprolineMonomyristin25-hydroxy-cholesterol3-Indoleacetic AcidGamma-L-Glutamyl-L-pipecolic acidDCITryptophyl-Arginine3-MethylindoleImidaprilatOleurosidePregnan-20-one, 17-(acetyloxy)-3-hydroxy-6-methyl-, (3b,5b,6a)-N6,N6-DimethyladenosineFormylisoglutamine6-Acetamido-3-oxohexanoatePE(17:0/0:0)1,2,4-NonadecanetriolTHTCProcurcumadiolPterinePE(14:0/18:3(6Z,9Z,12Z))JasmoloneAspartyl-TryptophanSoyasaponin IIILinoleoyl EthanolamideGamma-Glutamylproline(9Z,11E,13E,15Z)-4-Oxo-9,11,13,15-octadecatetraenoic acidGardoside(R)-2-Hydroxysterculic acidPC(14:0/18:1(11Z))1-heptadecanoyl-sn-glycero-3-phosphocholine1-(3-Hydroxy-5-methyl-2-thienyl)ethanonePyrrolidineGamma-GlutamylcysteinylserineArginyl-GlutamineTyrosyl-Glycine2-Hydroxymyristic acidPhosphocholine3-Deoxyguanosine13-Hydroxy-9-methoxy-10-oxo-11-octadecenoic acid25-Hydroxyvitamin D2-25-glucuronide2,6,6-Trimethyl-1-cyclohexen-1-acetaldehydeN1-AcetylspermineEpi-4'-hydroxyjasmonic acid2-MethylfuranAc-Arg-OHIsatinLysoPC(20:2(11Z,14Z))2-Propenyl octanoate3-Carboxy-4-methoxy-N-methyl-2-pyridonefalseMicrobial-derived Hyodeoxycholic Acid Ameliorates Painful Diabetic Neuropathy by Modulating Dorsal Root Ganglion TLR4-Mediated Neuroinflammation Signaling PathwayBACKGROUND: Painful diabetic neuropathy (PDN) is characterized by hyperalgesia and neuronal hyperexcitability. Although gut microbiota dysbiosis have been found in PDN, how microbiota influences PDN remains largely unexplored. RESULTS: Gut microbiota and its metabolites impacted PDN was investigated with multi-omics analyses in a rat model of high-fat diet/low-dose streptozotocin-induced type 2 diabetes. A significant decrease of the gut microbiota, including Clostridium, Lactobacillus and Bifidobacterium, as well as serum hyodeoxycholic acid (HDCA) was found in the PDN rats through 16S rRNA gene sequencing and metabolomics assessment, respectively. Transplantation of fecal microbiota from the PDN to normal rats resulted in the PDN phenotype, verified with the pain withdrawal threshold test and the whole-cell patch-clamp recordings of the dorsal root ganglion (DRG). Additionally, HDCA treatment was able to improve the hyperalgesia of PDN. RNA sequencing analysis, qRT-PCR, ELISA, Western blot and immunofluorescence revealed that HDCA mitigated neuroinflammation by inhibiting the TLR4/MyD88/NF-kappaB signaling pathway and reducing the production of proinflammatory cytokines in the DRG, thereby alleviating pain. CONCLUSIONS: Our data demonstrated that the microbiome-derived metabolite, HDCA, facilitated PDN through neuroinflammation inhibition. Overall, these findings provided a novel mechanism of PDN, and suggested that HDCA may have a therapeutic potential for 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