MetaboLightsapplication/xmlftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13006/m_MTBLS13006_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13006/m_MTBLS13006_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13006/s_MTBLS13006.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13006/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13006/a_MTBLS13006_LC-MS_negative_reverse-phase_metabolite_profiling.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13006/a_MTBLS13006_LC-MS_positive_reverse-phase_metabolite_profiling.txtprimary200OKftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS13006<p>Metabolite identification and quantification of the samples were performed based on a local metabolite database. The multiple reaction monitoring (MRM) chromatograms display all detectable metabolites within the samples, with each chromatographic peak represented by a different color corresponding to an individual metabolite. Characteristic ions of each metabolite were selected by the triple quadrupole mass spectrometer, and the ion intensities (counts per second, CPS) of these characteristic ions were recorded in the detector. The acquired raw files were processed using MultiQuant software, where chromatographic peaks were integrated and manually corrected as necessary. The peak area of each chromatographic peak represented the relative abundance of the corresponding metabolite, and the integrated peak area data for all metabolites were subsequently exported and saved.</p><p>To enable comparison of metabolite abundance across different samples, chromatographic peaks of each metabolite were aligned and corrected according to retention time and peak shape information, thereby ensuring the accuracy of qualitative and quantitative analysis. The figure below illustrates an example of quantification and alignment for a randomly selected metabolite across different samples, where the x-axis represents the retention time (min) and the y-axis represents the ion signal intensity (cps).</p>MetaboLightsPublicLiquid Chromatography MS - negative - reverse phaseLiquid Chromatography MS - positive - reverse phase<p>Sample extracts were analyzed using an LC-ESI-MS/MS system (UPLC: ExionLC AD; MS: QTRAP System). Analytical conditions: Waters ACQUITY UPLC HSS T3 C18 column (1.8 µm, 2.1 mm × 100 mm), 40 °C, 0.4 mL/min flow rate, and 2 μL injection. The solvent system was water (0.1% formic acid) and acetonitrile (0.1% formic acid) with a gradient: 95:5 V/V at 0 min, 10:90 V/V at 11.0 min, 10:90 V/V at 12.0 min, 95:5 V/V at 12.1 min, and 95:5 V/V at 14.0 min.</p>Omega-3 polyunsaturated fatty acids modulate gut microbiota-derived 18β-glycyrrhetinic acid to alleviate type 1 diabetes mellitus.The Fifth Affiliated Hospital, Sun Yat- sen UniversityYifan Guoblood serummass spectrometry assay<p>Briefly, samples were stored at -80 °C and then thawed on ice, before vortexed for 10 seconds. A 50 μL sample aliquot was combined with 300 μL of an extraction solution (ACN:Methanol, 1:4, V/V) containing internal standards. The mixture was vortexed for 3 mins and centrifuged at 12,000 rpm for 10 mins at 4 °C. A 200 μL supernatant was collected and kept at -20 °C for 30 mins before being centrifuged again at 12,000 rpm for 3 mins at 4 °C. Finally, 180 μL of the clarified supernatant was transferred for LC-MS analysis.</p>Mus musculushttps://www.ebi.ac.uk/metabolights/MTBLS13006Li Cong. The Fifth Affiliated Hospital, Sun Yat-sen University. Zhuhai 519000, Guangdong, China. congli@mail.sysu.edu.cn. +8607552528740.<p>Missing values were first imputed using the k-nearest neighbors (KNN) algorithm. Subsequently, the coefficient of variation (CV) was calculated for each metabolite in the QC samples, and only those with a CV value less than 0.3 were retained for downstream analysis. Mass spectrometry data processing was performed using Analyst software (version 1.6.3).</p><p>The figure below displays the Total Ion Chromatogram (TIC) of pooled quality control (QC) samples, which represents the summed intensity of all detected ions at each time point over the chromatographic run. Also shown is a Multiple Reaction Monitoring (MRM) multi-peak plot (i.e., extracted ion chromatogram, XIC), where the x-axis indicates the retention time (RT) of each detected metabolite, and the y-axis corresponds to ion signal intensity measured in counts per second (cps).</p>Treatmentguoyf2018@163.com<p>Fecal samples were collected from donor mice fed with an omega-3 PUFA-enriched diet or control diet. After broad-spectrum antibiotic treatment, recipient NOD mice underwent fecal microbiota transplantation (FMT) with freshly prepared fecal slurry resuspended in anaerobic sterile PBS. Serum samples were collected after FMT. All samples were snap frozen in liquid nitrogen and stored at −80°C until metabolomic analysis.</p>Metabolomicstype 1 diabetes mellitusuntargeted metabolitesOmega-3 Fatty Aciddiabetes mellitusgut microbiotaMacrophagetype 1 diabetes mellitusuntargeted metabolitesOmega-3 Fatty Aciddiabetes mellitusgut microbiotaMacrophage<p>Mass spectrometry was conducted on a QTRAP LC-MS/MS system with an ESI Turbo Ion-Spray interface, using both positive and negative ion modes. Key parameters: source temperature 500 °C, ion spray voltage 5500 V (positive) and -4500 V (negative), gas pressures at 55 psi (GSI), 60 psi (GSII), and 25 psi (CUR). Tuning and calibration used polypropylene glycol solutions, and MRM transitions were monitored for each metabolite.</p>N1,N8-diacetylspermidineLeu-Leu-GlyN'-Methyl-2-pyridone-5-carboxamide2'-O-methylcytidineIle-ThrCorticosteroneCaprolactamPyrocatecholCarnitine C14:2:DCPhe-IleEctoineThr-Val-Leu8,8a-deoxy-oleanePantothenol3-Methylcrotonyl GlycineProline-HydroxyprolineLPC(18:1/0:0)Thymoquinone(3,4-Dimethoxyphenyl) Acetic AcidGly-GluCarnitine C15:DCN-EthylglycineGly-Gln(R)-(-)-2-phenylglycine2',6'-Dihydroxy-4'-methoxyacetophenoneLPC(0:0/19:0)Trp-Ala-AspFurfuralAsn-Ile2-Methyl-1-PyrrolineCarnitine C6-OHJasmoneL-NIO-hydrochloride2'-O-MethylguanosineAla-PheL-TheanineN-Phenylacetylglycine1-Methylpiperidine-2-carboxylic acidCarnitine ph-C1Leu-Gly-LeuHexadecylamineMet-GluAllopregnanoloneN-Acetyl-L-HistidineProline betaineMG(18:1/0:0/0:0)OleamideLPC(20:4/0:0)1,4-Dihydro-1-Methyl-4-Oxo-3-PyridinecarboxamideCinnamic Acid3-(2-Hydroxyphenyl)propanoic acid4-Amino-5-hydroxymethyl-2-methylpyrimidinePro-GluSalicylaldehydeLPC(24:6e)Leu-ValSn-Glycero-3-PhosphocholineCarnitine C8-OH7-KetocholesterolAspartic Acid2,6-di-tert-butyl-1,4-benzoquinoneL-Ornithine5,6-Dihydroxyindole-2-Carboxylic AcidTrp-IleCarnitine C18:0Phe-GlyDamascenoneTyr-ThrCarnitine C18:3Carnitine C18:2Phe-GluCarnitine C18:1Ile-Gln5-Methoxytryptamine4-Methylhippuric AcidN(Alpha)-Acetyl-Epsilon-(2-Propenal)LysineGly-Ile2,4-QuinolinediolPyridineMethylguanidineLPC(22:5/0:0)Ala-AlaEthyl N-acetyl-L-tyrosinate4-Hydroxyquinoline3'-Adenylic acid2-PhenylglycineNorambreinolideCarnitine C3:1-2OH3-Methyladeninetrans-2-Butene-1,4-dicarboxylic AcidLPC(13:0/0:0)LPC(20:3/0:0)IndoleLPE(P-16:0)N-Acetyl-D-GalactosamineIle-GluGlu-Met6-hydroxyhexanoic AcidTyr-GlyLPA(20:0/0:0)L-ThyroxineAdenosineGlucosaminic acidCCT-018159AllopurinolUric acidPro-Ile2-Hydroxycinnamic acidMycosporine-glycineCarnitine C18:1-OHLPC(0:0/17:0)1-Aminocyclobutanecarboxylic acid1-desoxymethylsphinganineL-PhenylalanineAscorbic acidBromodeoxyuridine (BrdU)Trp-Glu2-pyrimidin-2-yl-propionic acid1-Hydroxylamino-2-phenylethane3,3',5-Triiodo-L-ThyronineS1P(d16:1)CAP-palmitateCarnitine C4-OHLPE(O-17:1)Carnitine C3:0Carnitine C9:1-OHIle-IleDL-Aminopimelic acidMethenamineLys-LeuEthyl-dodecanoategamma-Glu-PheAbietic acidSPH(d18:2)2-Thio-PAFLysine3-Indolebutyric AcidUrocanic Acid¦Ã-Glu-LysMG(20:4/0:0/0:0)Isoprenaline2-MethylbutyrylglycineNiclosamide4,5-Diaminofluorescein(DAF-2)Lys-Asp2-O-MethylcytosineGuanineQuinmeracLeu-MetPiperidoneLPC(16:0/0:0)Hyp-Trp5-Phenyl-1,3-oxazinane-2,4-dioneIndole-3-Carboxaldehyde1,3-DiaminopropaneXanthosine¦Â-Alanine(¡À)-Anabasine2'-Deoxycytidine-5'-MonophosphateCarnitine C20:1Carnitine C20:0Ala-ArgCarnitine C20:51-MethyladenineCytidine 5'-diphosphateCarnitine C20:4Carnitine C20:3Carnitine C20:28-MethylnonenoateMaleamic acid4-DeoxyuridineCarnitine C14:2-OHCork-oximate5,6-Dihydro-5-Methyluracil4-Pyridoxic AcidPhe-Val5-MethoxytryptophanN6-(4-hydroxybenzyl)adenine[(2R)-3-Hexadecoxy-2-hydroperoxypropyl] 2-(trimethylazaniumyl)ethyl phosphateCarnitine C5:1Carnitine C5:0Ala-ProLPE(P-18:1)2-Amino-2-deoxymannoseAsp-PheCyclo(Ala-Pro)Dehydroascorbic acidGeranic acidLPC(0:0/15:0)6-aminonicotinamideGly-ThrIndole-3-glyoxal2,4-DihydroxypteridineGuanidineDiisooctyl phthalateMyoinositolL-TryptophanamideN-AcetylcysteineDibutyl-phthalateOctadec-9-ene-1,18-dioic-acidN-Coumaroyl serotoninCarnitine C16:1-2OHThymineDL-Leucine1-MethyladenosineN(6),N(6)-Dimethyl-L-lysineSarcosineMethyl-L-alaninate2-Hydroxy-4-(methylthio)butyric acidCreosol(3beta,9xi,22S,23R)-3-Hydroxy-17,23-epoxyveratraman-11-oneMG(16:0/0:0/0:0)PE-NMe(16:1(9Z)/18:1(11Z))Trans-Zeatin1-Deoxyvaleric acidLPC(17:2/0:0)Pro-LeuN'-FormylkynurenineLPC(O-18:2)Methoxyindoleacetic AcidCarnitine C12:1Carnitine C12:0Gln-GlyCarnitine C16:1-OHTrigonellinePyridoxalN-Acetyl-Asp-GluLPC(16:1/0:0)Leu-Leu-LeuS1P(d18:2)(E)-GuggulsteroneLPC(20:2/0:0)FFA(22:7)Phe-MetN6-Succinyl AdenosineDiosbulbin B7-MethylguanosineUbiquinone-11-MethylguanosineCarnitine C15Tetrahydrocurcumin11-Aminoundecanoic acid4-Nitrophenyl 4-[bis(2H-1,3-benzodioxol-5-yl)(hydroxy)methyl]piperidine-1-carboxylateCalcitriolMalvidinAminolevulinic acid(R)-2-Hydroxy-3-phenylpropionic acidmethylcarbamyl PAFVal-IleEthyl 3-IndoleacetateL-TryptophanCarnitine C6:1Carnitine C6:0LPC(15:0/0:0)4-Guanidinobutyric AcidFFA(12:1)3-HydroxylidocaineCholesterol2-AminoadenosineTestosterone2-Hydroxy-6-Aminopurinen-Oleoylethanolamine3-aminobenzamideHexaethylene-glycolL-ValineUracil11-Dehydrocorticosterone2-Amino-4-methylphenol1-Methyl-hydantoinN,N-Bis(2-hydroxyethyl)dodecanamideDL-HomocysteineCarnitine C10:03-ChloroanilineLPC(0:0/22:4)EthylvanillinCarnitine C10:2Carnitine C10:1Glu-HisPro-AlaCytosineBiotinamideTyr-AsnTyr-AspGlycidyl-oleateLPC(0:0/12:0)Pro-PheL-Cystine3-HydroxyphenylureaHydroxyquinolineLPC(0:0/22:5)Asp-Arg3,6,9,12,15,18,21-Heptaoxatricosane-21,23-diolAla-His6-Methylthiopurine 5'-monophosphate ribonucleotideCarnitine C11:DC3-(Methylthio)-1-propanolKynurenic Acid2-Hydroxymuconic semialdehydeCarnitine C8:121-DeoxycortisolCarnitine C8:0Carnitine ph-C14HydroxyureaS1P(d18:1)LPC(0:0/22:2)LPC(18:0/0:0)Phe-Val-AspNicotinuric AcidSer-ProFFA(20:6)S-(5-Adenosy)-L-HomocysteineNADP+LPC(22:4/0:0)2'-Hydroxy-5'-methylacetophenoneFructose8-Hydroxy-2-DeoxyguanosineCyromazineTyr-LeuN-Acetylaspartate(R)-(-)-1-Amino-2-propanolAsp-Leu(-)-IsopulegolNicotinamide-N-Oxide1-Methylinosine5-Aminoimidazole-4-carboxamideAndrostenediol2-Pyrrolidineacetic acidThiamine-MonophosphateN¦Á-Acetyl-L-ArginineHistidineCarnitine C16:2Carnitine C16:1Ser-PheCarnitine C16:0L-PhenylalaninolCarnitine C16:32-Amino-3-phosphonopropionic acidLPC(18:4/0:0)L-CitrullineCarnitine C16-OHalpha-AsaroneGly-ValThr-Aspcyclo(leu-phe)DihydrojasmoneMelezitose3-Methoxyphenylacetic acidN4-AcetylcytidineLinoleylethanolamideLeu-Val-SerCis-4-Hydroxy-L-ProlineErgothioneine4-tert-butylbenzoic acidTripropylamineTyr-ProLPC(0:0/20:3)Quinoline-4-carboxylic acidDesoxycortoneLPC(0:0/20:4)5-MethylfurfuralMG(0:0/22:6/0:0)Xanthurenic AcidN-methyl-4-aminobutyric acid2-Methylguanosine2,4-diacetamino-2,4,6-triphenoxy-D-mannopyranoseIle-MetInositol 1,3,4-trisphosphateLys-Ser3-O-MethyldopaGlu-Phe-AlaCarnitine C20:1-OHLPC(0:0/20:5)Di-n-propyl-phthalateHeptethylene-glycolCholinePC(8:0/8:0)3-Amino-2-naphthoic acidTrp-ProSDMA9-Fluorenol7,8-dihydro-L-Biopterin1-Aminopropan-2-olL-IsoleucineLPC(0:0/20:1)Carnitine C6-2OHAnilineCarnitine C14:0Carnitine C14:3Carnitine C14:2Carnitine C14:1Val-Glu7-MethylxanthineAla-Lys2-Aminopurine3-Amino-4-methylpentanoic acidL-IsoserineLPC(20:5/0:0)LPC(0:0/20:2)Pro-AsnMethyl-p-tert-butylphenylacetate2'-DeoxyadenosineGln-PheL-Dihydroorotic AcidN-Methyl-D-Aspartic AcidN-(2-hydroxyethyl)-3-pyridinecarboxamideDiethyl-2-methyl-3-oxosuccinate10-Formyl-Thf5-Methyl-2'-deoxycytidinePhe-HypDihydrokavainCarnitine C17:1:DC2-Phenylpropylamine2-(Dimethylamino)Guanosine1-Octadecyl-2-acetyl-sn-glycero-3-phosphocholineS-Methyl thioacetatePiperidineD-OrnithineCarnitine C18-OHIsocytosine3-Guanidinopropionic acidPhosphocholineTrp-Asp3-Aminoquinoline5-Hydroxypyridine-2(1H)-one7-Amino-4-methylcoumarinPregnanetriolEstrone1,7-DimethylxanthineLPC(20:0/0:0)RiboflavinLPC(19:2/0:0)OxidopamineIle-Lys11-Beta-hydroxyandrostenedione2-Hydroxy-2-methylbutanenitrileGlu-LeuLPC(0:0/18:2)Indole-3-Acetic AcidLPC(16:3/0:0)Lys-ValCarnitine C14:1-OHLPC(14:1/0:0)Cyclo(Pro-Glu)BiotinLPC(22:2/0:0)L-ProlineUreaLeu-AsnLPC(0:0/18:3)Methyl beta-D-galactopyranosideN-MethyTrans-4-Hydroxy-ProlineN1-AcetylspermidineGlucosamine3-Methylthiopropylamine5-Aminoimidazole ribonucleotide3-Aminobenzenesulfonic acidCarnitine C18:2-OHLPC(0:0/18:0)LPC(O-14:0)(4Z,7Z,10Z,13Z,16Z,19Z)-EicosahexaenoateBenzylcinnamateFarnesylacetoneCarnitine C14-OHMethylcysteine3-(3,4,5-trimethoxyphenyl)propionic acidP-Coumaric AcidN-AcetylcadaverineLPC(O-14:1)LPC(0:0/18:1)8-AzaguanineAsp-LysGuanosineS-Adenosyl-L-Methionine4-Acetamidobutyric AcidO-Phospho-L-tyrosine2-AminomethylpyrimidineChaps5-OxoprolineArainosineLys-Ile3-Amino-2-piperidinoneDiethyl-phosphateLPC(22:3)3-N-Methyl-L-Histidine1-MethylguanineGlu-Phe(2E,4E)-6-(2-aminophenyl)-2-hydroxy-6-oxohexa-2,4-dienoic acid5-Aminosalicylic AcidPhenethylamineHuperzine A11-Cis-RetinolIsoxanthopterinPhe-SerDiethanolamineLPC(0:0/16:2)Gly-HisThiamineCarnitine C19:1N-Methyl-¦Á-aminoisobutyric acidN-MethyltryptamineGlutathione ReducedformIle-SerTrp-HisSuberylglycineMG(18:2/0:0/0:0)3-Iodo-L-TyrosineMethyl-2-pyrrolidone-5-carboxylateL-Tyrosine1-NaphthylamineN6-(2-Hydroxyethyl)adenosinePhe-ProAurapteneMannoseN6-Acetyl-L-LysineHexadecanalLPC(O-16:0)SpermidineCortexoloneTriethylamine1-acetylindoleN,N-diacetyl-O-methylhydroxylamineLeu-AlaLPC(0:0/16:0)PC(O-1:0/O-16:0)3-(imidazol-4-yl)propionic acidFolinic acid2-Indanone oximeLPE(P-17:0)Glycerol-TributyrateAmmeline(2S,3S)-butane-2,3-diolDioctyl phthalateRibitolLPC(O-16:1)2-((3-Oxo-3-phenylpropyl)amino)acetic acid(2-Hydroxyethyl)phosphonic acidLPC(0:0/16:1)2'-Deoxycytidine-5'-DiphosphateLPC(12:0/0:0)MesoxalateArg-Glu5-Methylcytidine4-Hexylaniline3-Indole carboxylic acid glucuronideHydroxyacetoneURB9372,6-Dihydroxybenzoic acidm-CresolCarnitine C2:07alpha,26-Dihydroxy-4-cholesten-3-oneCreatinineButylamineCarnitine isoC4:0Carnitine C5:DCPimelic acid3,4-Dichloroaniline2-PhenylacetamideN,N-DimethylformamideMG(0:0/20:4/0:0)LPC(20:1/0:0)Thr-GluCyclo(Phe-Pro)AstaxanthinButyl-3-methylbutanoateTheobromineUrobilinLeu-LeuBetaineL-AlaninePalmitoylethanolamide£¨PEA£©Glu-TyrN-(3-Indolylacetyl)-L-alanineCarnitine C12-OHPro-SerCytidineCyclo(Ser-Pro)2-FuroylglycineSPH(d17:1)L-PhenylephrineIsoquinolineConiferolN-HydroxytyrosineCarnitine C18:1:2DCAzelaoyl PAF4-HydroxytryptamineGly-Lys1-MethylhistidineTriphenyl-phosphateVal-Leu¦Ã-Aminobutyric AcidArg-IleLPC(17:0/0:0)Carnitine C4:0N-MethylalanineLeu-ArgRibosyladenosineS-methyl-L-thiocitrullineLPC(0:0/14:0)LPC(19:1/0:0)2,2-Dihydroxymethyl-1-azabicyclo[2.2.2]octan-3-onePhe-Ala-SerCarnitine C5-OH3-(4-Hydroxyphenyl)-Propionic AcidLPC(16:2/0:0)ST-638cyclo(pro-pro)7-Methyluric AcidLPC(0:0/14:1)Isonicotinic acid5-Acetylamino-6-amino-3-methyluracilMG(20:5/0:0/0:0)Ile-Asp1-AminopentadecaneIle-Asn4-Amino-3-hydroxybutyric acidCarnitine C7:1Ala-Val4-Chloroaniline2,5-Dimethyl-2,3-dihydrofuran-3-oneMG(0:0/20:5/0:0)SPH(d16:1)6-Diazo-5-oxo-L-norleucineL-SaccharopineCarnitine C7:0Phosphoenolpyruvate3-AminophenolN-FormylmethionineAsn-Met3-Hydroxy-L-phenylalanineLPC(18:3/0:0)Indole-5-carboxylic acidTetraethylene-glycolPalmitoylethanolamide2'-DeoxyinosineGly-LeuGuanidineacetic AcidBarbituric acidMG(22:6/0:0/0:0)Leu-Thr2,4-DihydroxypyridineN¦Á-Acetyl-L-glutamineDopaquinoneN-acetylpyrrolidineCaldineTrimethylamine-N-OxideCocamidopropyl betaine1-AziridineethanolLPC(O-20:0)Butenoyl-PAFN-Formylglycine3-MethoxytyramineLPC(19:0/0:0)LinoleamideCarnitine C13:1L-NorleucineCarnitine C13:0D-AlloisoleucineLys-Phe3-Methyladipic acid4-Hydroxy-4-(pyridin-2-yl)butan-2-oneN-Acetyl-D-GlucosamineSerotoninP-HydroxydiphenylamineSecurinine2-(Formylamino)Benzoic AcidCycloleucine4-(4-Hydroxyaniline)-6,7-DimethoxyquinazolinePhe-Leu2-Picolinic AcidLPE(0:0/15:0)L-HomocitrullineCarnitine C24:5N-AcetylmannosamineHeterodendrinGlu-Gly6-O-methylguanineCarnitine C24:6Carnitine C9:0Carnitine C4:DC2,5-Dihydroxyacetophenone18¦Â-Glycyrrhetinic acidLPC(24:6/0:0)3-Hydroxy-2-methyl-4H-pyran-4-oneIle-Leu5'-Deoxy-5'-(Methylthio) AdenosineSer-ValOctadecadienamide2-Acetyl-5-methylfuranLys-Ala16-DehydroprogesteroneHypoxanthineN6-methyladenosineMethyl caffeate2-Phenylpropionic acidcis-CitralPutrescineN-acetyl-D-LactosaminePro-Met11-Carbonyl-beta-acetyl-boswellic acidPhe-AspCarnitine C12:1-OHCytarabine3-Methylequuric acidCarnitine C11:12,6-Diamino-5-hydroxyhexanoic acidCarnitine C11:0N6,N6,N6-Trimethyl-L-lysine5-MethyluridineN-(3-Hydroxypropyl)phthalimideD-Glucono-1,5-LactoneAdenineGlu-Ile5-Hydroxy-L-TryptophanGly-PheCarnitine C22:3Carnitine C22:2Carnitine C22:1L-SerineCarnitine C22:6PurineCarnitine C22:4Ile-ArgN-Tetradecanoyl-L-homoserine lactoneLumichrome2-PyrrolidinoneN-acetyl-D-phenylalanine10-deoxyformamycin2-Pentyl-3-phenyl-2-propenalLPC(18:2/0:0)2'-O-methyladenosineLys-Gly5-Aminovaleric AcidUreidosuccinic acidPseudotropineArg-MetShinorineTrans-Cinnamaldehyde6-MethylnicotinamideCaffeine2-((4-Amino-2-nitrophenyl)amino)ethanol(1R,6S)-6-amino-5-oxocyclohexyl-2-ene-1-carboxylic-acid-esterMaltotrioseMethyl Indole-3-AcetateL-Methioninealpha-CEHCDihydrouracilN-Amidino-L-AspartateN-AcetylhistamineNicotinamideColneleic acidTheophylline6-Aminocaproic Acid2-Hexadecanoylthio-1-ethylphosphorylcholineCyclo(Pro-Val)Maslinic acidBovinic acidAcrylamideSer-Phe-AlaPiperazineCarnitine C17:1Carnitine C17:07alpha-Hydroxy-3-oxo-4-cholestenoic acidGly-Gly-PheAsp-IlePyr-GluLPC(17:1/0:0)EDTA20,26-dihydroxyecdysoneL-Norvaline7-(alpha-D-glucosyl)-N(6)-isopentenyladenineAcetylcholineCyclo(Phe-Glu)2-(3,4-dimethoxyphenyl)ethanamineLeu-GluThymidinePC(12:0/12:0)Menadione-9Indole-3-acetamideLPC(O-20:2)2-Methyl-5-nitroimidazole-1-ethanolFK-409N,N-DimethylarginineLPC(22:6/0:0)2,3-dimethylmaleic-anhydride18-HydroxycorticosteroneBenzaldehyde1-Fluorocyclohexadiene-cis,cis-1,2-diolMonoisobutyl-phthalateHistamineCyclo(Pro-Phe)1-methylhistamineLPC(O-20:3)2,6-Diaminopimelic acidNicotinic Acid4-Aminomethylpyrimidinealpha-hexylcinnamaldehydeTraumatin2-Hydroxyadenosine6-DimethylaminopurineOxypurinolLPC(14:0/0:0)Pterine1,3-DicyclohexylureaHexadecanamideRaffinoseGly-TyrO-Acetyl-L-homoserineL-Glycine2-Amino-2-methyl-1,3-propanediolL-CarnosineCarnitine C15:1PyrrolidineGlu-CitL-TyrosinamideCyclopentylglycine2,22-Dideoxy-3-dehydroecdysoneTriethyl-phosphate2-Butyl-3-(4-hydroxybenzoyl)benzofuranCarnitine-2-methyl-C4SynephrineDeoxycytidinePhe-AlaLeu-Gly3,4,5-Trimethoxycinnamic AcidfalseOmega-3 polyunsaturated fatty acids modulate gut microbiota-derived 18β-glycyrrhetinic acid to alleviate type 1 diabetes mellitus<p>Background</p><p>Omega-3 polyunsaturated fatty acids (PUFAs) are known to protect against type 1 diabetes mellitus (T1DM), but how they act through the gut-islet axis is not fully understood. This study explored how Omega-3 PUFA-influenced gut microbiota and their metabolites help protect pancreatic islets in T1DM. The objective of this study was to determine whether gut microbiota and its metabolites sever as mediators of the protective effect of Omega-3 PUFAs and to elucidate the underlying mechanisms.</p><p>Methods</p><p>We used fecal microbiota transplantation (FMT) to test the effects of Omega-3 PUFA-derived gut microbiota in NOD mice. Immune cell changes in the islets were analyzed using transcriptomics, flow cytometry, and immunohistochemistry. Metabolomics identified key metabolites in serum related to gut microbiota changes. Co-culture experiments examined the role of specific metabolites in macrophage polarization and β-cell function.</p><p>Results</p><p>Omega-3 PUFA-treated and FMT mice showed reduced islet inflammation and an increased abundance of the Eubacterium coprostanoligenes group. Enhanced M2 macrophage polarization was observed in the islet microenvironment of FMT mice. Among gut microbiota metabolites, 18β-glycyrrhetinic acid (18β-GA) was strongly linked to E. coprostanoligenes and stood out as a key molecule. In co-culture experiments, 18β-GA shifted macrophages to an M2 phenotype, which boosted insulin production and secretion in β-cells.</p><p>Conclusions</p><p>Omega-3 PUFA-derived gut microbiota and the metabolite 18β-GA play a key role in protecting pancreatic islets in T1DM by modulating macrophage polarization and improving β-cell function. These findings suggest new ways to use gut microbiota for T1DM treatment.</p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