The 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.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - negative - reverse phase","Liquid Chromatography MS - positive - reverse phase"],"chromatography_protocol":["The 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.
"],"publication":["Microbial-derived Hyodeoxycholic Acid Ameliorates Painful Diabetic Neuropathy by Modulating Dorsal Root Ganglion TLR4-Mediated Neuroinflammation Signaling Pathway."],"submitter_name":["Ye Jiang"],"submitter_affiliation":["Peking university third hospital"],"organism_part":["blood serum"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["Briefly, 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.
"],"organism":["Rattus norvegicus"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS12087"],"author":["Yongzheng 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."],"data_transformation_protocol":["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.
"],"study_factor":["RF treatment","Biological replicate"],"submitter_email":["jyeaho@163.com"],"sample_collection_protocol":["Rats were euthanized, and blood was collected for serum extraction.
"],"omics_type":["Metabolomics"],"study_design":["ultra-performance liquid chromatography-mass spectrometry","pooled quality control sample","untargeted analysis","Thermo Scientific Q Exactive HF-X","Rattus norvegicus","blood serum","untargeted metabolites","Thermo Scientific Vanquish Horizon UHPLC System","Diabetic Neuropathies","Intestinal Flora","experimental sample"],"curator_keywords":["ultra-performance liquid chromatography-mass spectrometry","pooled quality control sample","untargeted analysis","Thermo Scientific Q Exactive HF-X","Rattus norvegicus","blood serum","untargeted metabolites","Thermo Scientific Vanquish Horizon UHPLC System","Diabetic Neuropathies","Intestinal Flora","experimental sample"],"mass_spectrometry_protocol":["The 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.
"],"metabolite_name":["Soyasapogenol B 3-O-b-D-glucuronide","(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(6-imino-1-methylpurin-9-yl)oxolane-3,4-diol","Alpha-CEHC glucuronide","P-CHLOROPHENYLALANINE","Xestoaminol C","13(S)-HOTrE","5-Aminopentanamide","Succinoadenosine","N1,N12-Diacetylspermine","N-di-Demethyl roxithromycin","Caffeic Acid","Indolylacryloylglycine","Cumene","11-bromo-undecanoic acid","2-Pyridylacetic acid","L-gamma-glutamyl-L-valine","6-[5]-ladderane-1-hexanol","1-Kestose","Phenylalanylproline","Arginyl-Leucine","Hyocholic acid","Hercynine","6-[1-carboxy-2-(4-methoxy-1-benzofuran-5-yl)-2-oxoethyl]-3,4,5-trihydroxyoxane-2-carboxylic acid","N1-Acetylspermidine","PGF2a ethanolamide","20,24-Epoxy-25,26-dihydroxydammaran-3-one","5-Hydroxyindoleacetic acid","Gingerglycolipid B","Gingerglycolipid C","Glyceryl 5-hydroxydecanoate","3,3'-Dihydroxy-4',5,7-trimethoxyflavan","Kinetensin 4-7","(+/-)7-epi Jasmonic Acid","Imidazole lactate","Furaneol 4-(6-malonylglucoside)","Jasmone","3-Methoxytyrosine","15d PGD2","{[1-(4-methoxyphenyl)pentan-3-yl]oxy}sulfonic acid","Stearoylethanolamide","3,4-Dimethylstyrene","Estriol","D-erythro-Sphingosine C-17","Tetraphyllin B","D-erythro-Sphingosine C-15","Valyl-Lysine","L-phenylalanyl-L-proline","N2-Succinyl-L-glutamic acid 5-semialdehyde","Trans-4-Coumaric acid","Hydroxysafflor yellow A","3,3',4',7-Tetrahydroxyflavone","N-Acetylcadaverine","LysoPE(0:0/18:2(9Z,12Z))","Temazepam","4-Methyl-5-thiazoleethanol","LysoPE(16:1(9Z)/0:0)","Oleamide","6-({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 acid","3-Hydroxydodecanedioic acid","PE(16:0/0:0)","Kainic acid","Dehydrocarpaine I","N-Nitrosoguvacoline","4-Pyridoxic acid","3,4,2',4',6'-Pentahydroxychalcone","Butoctamide hydrogen succinate","N-Succinyl-L-glutamate","Ribothymidine","(-)-Glycinol","6-[(E)-2-(2H-1,3-benzodioxol-5-yl)ethenyl]-5-hydroxy-4-methoxy-5,6-dihydro-2H-pyran-2-one","umbelliferone","Tyrosyl-Aspartate","3-Oxocholic acid","LysoPC(18:1(11Z))","2-Formaminobenzoylacetate","Neuromedin B (1-3)","Dioscoretine","Prolylphenylalanine","Soyasaponin IV","Cotinine glucuronide","Methyl beta-D-glucopyranoside","Homoveratric acid","Aminoadipic acid","Porson","Hydroxyprolyl-Leucine","2-Indolecarboxylic acid","(2S)-2-{[1-(R)-Carboxyethyl]amino}pentanoate","ethoxyquin","3-(4-hydroxyphenyl)acrylic acid","2'-Apo-beta-carotenal","C12:4n-2,4,8,10","1H-Indol-3-ylacetyl-myo-inositol","Glutaminylhydroxyproline","L-Thyronine","1-Methylguanine","(R)-Serine","Meta-O-Dealkylated flecainide","Glutamylproline","C16 Sphingosine","Isopropyl hexadecanoate","3a,7b,21-Trihydroxy-5b-cholanoic acid","Valyl-Tyrosine","4-Hydroxyproline galactoside","Glaudine","6-Hydroxyindolelactate","4-PIOL","LysoPC(20:3(5Z,8Z,11Z))","5-Methyl-2-furaldehyde","L-Hisidine","Gamma-Glutamylisoleucine","Methyl-delta-ionone","Cysteinyl-Glutamine","Palmitoleamide","26-Glucosyl-1,3,11,22-tetrahydroxyergosta-5,24-dien-26-oate","(-)-Epinephrine","9-OxoODE","N-Acetyl-L-glutamic acid","Isovalerylglutamic acid","4-Isopropylbenzoic acid","Ketoisophorone","Asterosterol","3-O-Acetylepisamarcandin","3-Pyridinebutanoic acid","2-Hydroxycinnamic acid","cresopyrine","6b-Hydroxy-8a-methoxy-7(11)-eremophilen-12,8-olide","2-Hydroxy-6-oxo-6-phenylhexa-2,4-dienoate","Tyrosyl-Proline","Isopentenyl adenosine","3,7-Dimethyl-8,11-dioxo-2E,6E,9E-dodecatrienal","Alpha-Methylstyrene","3-Hydroxycinnamic acid","Pinolenic Acid","Humulol","Glycylproline","Kudzusaponin SA2","Kudzusaponin SA1","LysoPE(20:4(5Z,8Z,11Z,14Z)/0:0)","N-(3-Aminopropyl)morpholine","Musabalbisiane C","2-(4-Methoxyphenyl)acetic acid","3-hydroxyundecanoyl carnitine","Urocanic acid","20-trifluoro-LTB4","Oblongolide","2-Methylindoline","N-acetyl-4-aminosalicylic acid","C1'-C9-Glycosylated UWM6","8-(1,2-dihydroxypropan-2-yl)-2-oxo-2H,8H,9H-furo[2,3-h]chromen-9-yl 3-methylbut-2-enoate","Phenylacetaldehyde","Asperagenin","N-Acetylglucosamine","Curcumenol","(4R,6S)-p-Menth-1-ene-4,6-diol 4-glucoside","citropten","2-Indanone","LysoPC(16:1(9Z)/0:0)","N-Acetyl-4-O-acetylneuraminic acid","Hovenine A","Serratol","2-Phenylethyl octanoate","Octadecanamide","1-Linoleoylglycerophosphocholine","Herculin","2-Ethylacrylic acid","Cavinine","D-Pantethine","Pimelic acid","Metabolite M6","Yucalexin P17","N,N'-bis(3-aminopropyl)butane-1,4-diamine","3-Formyl-6-hydroxyindole","Histidinal","Succinylmonocholine","Palmitic amide","DG(18:4(6Z,9Z,12Z,15Z)/18:3(6Z,9Z,12Z)/0:0)","2-Amino-3-carboxymuconic acid semialdehyde","10,20-Dihydroxyeicosanoic acid","Glutaminyl-Hydroxyproline","5-Methoxytryptophan","Yucalexin P15","L-Urobilinogen","Carboxyprimaquine","6-Lactoyltetrahydropterin","Indole-3-carboxaldehyde","Stearic acid","4-(aminomethyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol","7,8-Dihydro-3b,6a-dihydroxy-alpha-ionol 9-[apiosyl-(1->6)-glucoside]","Jasmonic acid","Gamma-Glutamyl-S-methylcysteine sulfoxide","Alpha-Aspartyl-lysine","C14:5n-1,3,5,7,9","Pisumionoside","Discadenine","L-Methionine S-oxide","LysoPC(18:0)","Aphidicolin","N2-Malonyl-D-tryptophan","Taurochenodeoxycholic acid","Diacetyldideisovaleryl-Rhodomyrtoxin","Trimethylamine N-oxide","Isoleucyl-Hydroxyproline","2-[2,4,6-trihydroxy-3-(3-methylbut-2-en-1-yl)phenyl]acetic acid","Genipin","1,4-Methylimidazoleacetic acid","3-ketosphinganine","4-oxo-1H-quinoline-2-carboxylic acid","Pyridine N-oxide glucuronide","4-Hydroxy-4-(3-pyridyl)-butanoic acid","Deoxydihydro-artemisinin","Mycosporine","4-Pyrimidine Methanamine (hydrochloride)","KAPA","Gamma-L-Glutamyl-gamma-L-glutamyl-L-methionine","1-Oxo-1H-2-benzopyran-3-carboxaldehyde","Thymine","L(-)-Pipecolinic acid","9R,10S-Epoxy-3Z,6Z-eicosadiene","4-methoxybenzene-1,3-diol","PE(14:0/0:0)","7-Ketolithocholic Acid","(2'E,4'Z,7'Z,8E)-Colnelenic acid","Farnesyl acetone","D-Urobilinogen","Ethyl 3-hydroxydodecanoate","2-Formyloxymethylclavam","Beta-Ionol","Isonicotinic acid","Cynaratriol","Gamma-Glutamyl-beta-aminopropiononitrile","1-Methylhistamine","Acetylshikonin","Gamma-Glu-Leu","24-Hydroxycalcitriol","PE(P-16:0/14:1(9Z))","12-ketolithocholic acid","(S)-methoprene","Trigoforin","(4E,8E,10E-d18:3)sphingosine","Camellenodiol","Cyclododecanone","Adenosine 3'-monophosphate","Alpha-Vetivone","10-Epijunenol","P-Mentha-1,3,5,8-tetraene","Palmitoylethanolamide","(17alpha,23S)-17,23-Epoxy-29-hydroxy-27-norlanosta-1,8-diene-3,15,24-trione","L-L-Homoglutathione","3''-Deamino-3''-oxonicotianamine","Gibberellin A12","Citreoviridin C","7,8-dihydroxy-4-methyl-coumarin","Dopamine glucuronide","4-Hydroxy-2,6,6-trimethyl-3-oxo-1,4-cyclohexadiene-1-carboxaldehyde","Leucyl-Valine","5,7-dihydroxy-2-(4-hydroxyphenyl)-6-methoxy-chromone","(3beta,17alpha,23S)-17,23-Epoxy-3,28,29-trihydroxy-27-norlanost-8-en-24-one","CD 1790","L-phenylalanyl-L-hydroxyproline","Lysyl-Lysine","1-Methylguanosine","L-Pyridosine","(E)-2-Tridecene-4,6,8-triyn-1-ol","Fluprostenol Lactone Diol","3,5,5-Trimethyl-3-cyclohexen-1-one","Celastrol","Caryophyllene oxide","Malvidin","Feruloylputrescine","Withaperuvin E","N-methylisoleucine","LysoPC(P-16:0)","PA(15:0/22:4(7Z,10Z,13Z,16Z))","2-Hydroxy-7,8-dehydrograndiflorone","Miraxanthin-V","Methyl 2-undecynoate","Niacinamide","Casticin","Eupacunolin","Trolamine","Uracil","Eicosapentaenoic acid","Melleolide","Lagerstroemine","(2S)-2-amino-3-[4-hydroxy-3-(sulfooxy)phenyl]-2-methylpropanoic acid","Creatine","(S)-(-)-Perillyl alcohol","16-Hydroxy hexadecanoic acid","L-Glutamic Acid","Heptadecanoyl Ethanolamide","Hypoglycin B","DHAP(10:0)","DL-Citrulline","2-Amino-4-oxo-4-alpha-hydroxy-6-(erythro-1',2',3'-trihydroxypropyl)-5,6,7,8-tetrahydroxypterin","N-heptanoyl-homoserine lactone","Cytosine","Leridol","Indoleacrylic acid","Ferulic Acid","4-[5]-ladderane-butanoic acid","Niazimin A","Ricinoleic Acid methyl ester","Threoninyl-Gamma-glutamate","(3S,7E,9S)-9-Hydroxy-4,7-megastigmadien-3-one 9-glucoside","Dinor-PGE2","(3b,4b,11b,14b)-11-Ethoxy-3,4-epoxy-14-hydroxy-12-cyathen-15-al 14-xyloside","Succinic acid","23-trans-p-Coumaroyloxytormentic acid","Hippuric acid","3'-Amino-3'-deoxythimidine","21-Deoxycortisol","LysoPC(0:0/18:0)","MG(15:0/0:0/0:0)","4-Hydroxy-2-quinolone","D-Pipecolic acid","(1alpha,3beta,20S,22R,24S,25S)-Pubescenin","Cytarabine","Homovanillic acid","L-(-)-Tyrosine","N-Succinyl-L,L-2,6-diaminopimelate","Haemanthidine","2-Aminobut-2-enoate","Methylgingerol","Oxindole","Hexyl glucoside","Corchorosol A","1-pentadecanoyl-glycero-3-phosphate","2-Hydroxyphenethylamine","7-Tridecynoic acid","Ethyltestosterone","6-O-Methylguanine","(3beta,5alpha,9alpha,14alpha,22E,24R)-3,5,9,14-Tetrahydroxyergosta-7,22-dien-6-one","Lumichrome","2-Pyrrolidinone","Aminohydroquinone","PC(16:0/0:0)[U]","Corchorifatty acid F","N-Acetyl-L-phenylalanine","PS(O-16:0/0:0)","22-Angeloylbarringtogenol C","Tauro-alpha-muricholic acid","4-Hydroxymedicarpin","M-Coumaric acid","Ascochitin","4-Hydroxycinnamic acid","P-Tolualdehyde","11-keto Fluprostenol","2,5-Dimethylbenzaldehyde","9,12,15-Octadecatrien-1-ol","PERICIAZINE","L-phenylalaninol","(S)-5-Amino-3-oxohexanoate","6E,8E,12E,14E-Hexadecatetraen-10-ynoic acid","Chalcolactone","Soyasaponin I","Neryl butyrate","5-(2'-Carboxyethyl)-4,6-Dihydroxypicolinate","Cassythine","Soyasaponin V","N4-Acetylcytidine","6-Hydroxyetodolac","Corchorifatty acid D","Lucidone C","6-O-Acetylaustroinulin","10,12-Tetradecadiene-4,6-diynoic acid, (E,E)-","4-formyl Indole","Avocadene 4-acetate","(R)-3-Hydroxybutyric acid","(R)-Mandelamide","N-Acetyltyramine","P-Hydroxybenzaldehyde","Betaine aldehyde","(+/-)-Ibuprofen","1-Pyrroline","2-Methylguanosine","7,12-Dihydroxy-3,11,15,23-tetraoxolanost-8-en-26-oic acid","Vulgarone A","4-Androstenediol","L-Glutamine","6,7-dihydro-12-epi-LTB4","Lepadin D","1-(1,2,3,4,5-Pentahydroxypent-1-yl)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylate","(+)-15,16-Dihydroxyoctadecanoic acid","Fisetin 8-C-glucoside","LysoPC(20:4(8Z,11Z,14Z,17Z))","Oryzalic acid B","N-Decanoylglycine","Guaiazulene","Dihydrocaffeic acid 3-sulfate","AH 6809","thymoquinone","2,6-Piperidinedicarboxylic acid","Indole-3-acetamide","Boviquinone 4","11-Hydroxyeicosatetraenoate glyceryl ester","Phenylpropionylglycine","Lyso-PAF C-16","12,13-EpOME","N-Arachidonoyl-3-hydroxy-gamma-Aminobutyric Acid","Glabrene","Succinylproline","Monomyristin","25-hydroxy-cholesterol","3-Indoleacetic Acid","Gamma-L-Glutamyl-L-pipecolic acid","DCI","Tryptophyl-Arginine","3-Methylindole","Imidaprilat","Oleuroside","Pregnan-20-one, 17-(acetyloxy)-3-hydroxy-6-methyl-, (3b,5b,6a)-","N6,N6-Dimethyladenosine","Formylisoglutamine","6-Acetamido-3-oxohexanoate","PE(17:0/0:0)","1,2,4-Nonadecanetriol","THTC","Procurcumadiol","Pterine","PE(14:0/18:3(6Z,9Z,12Z))","Jasmolone","Aspartyl-Tryptophan","Soyasaponin III","Linoleoyl Ethanolamide","Gamma-Glutamylproline","(9Z,11E,13E,15Z)-4-Oxo-9,11,13,15-octadecatetraenoic acid","Gardoside","(R)-2-Hydroxysterculic acid","PC(14:0/18:1(11Z))","1-heptadecanoyl-sn-glycero-3-phosphocholine","1-(3-Hydroxy-5-methyl-2-thienyl)ethanone","Pyrrolidine","Gamma-Glutamylcysteinylserine","Arginyl-Glutamine","Tyrosyl-Glycine","2-Hydroxymyristic acid","Phosphocholine","3-Deoxyguanosine","13-Hydroxy-9-methoxy-10-oxo-11-octadecenoic acid","25-Hydroxyvitamin D2-25-glucuronide","2,6,6-Trimethyl-1-cyclohexen-1-acetaldehyde","N1-Acetylspermine","Epi-4'-hydroxyjasmonic acid","2-Methylfuran","Ac-Arg-OH","Isatin","LysoPC(20:2(11Z,14Z))","2-Propenyl octanoate","3-Carboxy-4-methoxy-N-methyl-2-pyridone"],"additional_accession":[]},"is_claimable":false,"name":"Microbial-derived Hyodeoxycholic Acid Ameliorates Painful Diabetic Neuropathy by Modulating Dorsal Root Ganglion TLR4-Mediated Neuroinflammation Signaling Pathway","description":"BACKGROUND: 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 PDN.
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