MetaboLights

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data files generated by LC-MS/MS were processed with SCIEX Analyst Work Station Software (1.7.3), metabolites quantification was analyzed with automation analysis software BIOTREE BioBud (v2.0.4).MetaboLightsPublicLiquid Chromatography MS - alternating - reverse-phaseFor RP system, The LC separation was carried out using an UPLC System (Agilent 1290 UPLC), equipped with a ACQUITY UPLC BEH C18 Column (1.7 µm, 2.1 mm × 150 mm). The mobile phase A was 0.1% FA in H2O, and the mobile phase B was mixed H2O and MeOH (5:95) containing 10 mmol/L ammonium formate. The auto-sampler temperature was set at 6 ∘C and the injection volume was 1 μL.Enterotoxigenic Bacteroides fragilis exacerbates alcoholic liver disease progression through kynurenine mediated AMPK signaling inhibition and retinoic acid depletion.Daya ZhangHainan medical universityserummass spectrometry assayThe samples were thawed in ice water bath and was vortexed for 30s. 100 μL of liquid samples was mixed with 400 µL methanol containing internal standard and were vortexed for 30 s. After sonication in ice-water bath for 15 min, samples were incubated at -40 ∘C for 1 h. Then the samples were centrifuged at 12000 rpm and 4 ∘C for 15 min, 200 μL supernatant of each sample was transferred to glass vial for LC-MS/MS analysis. Pool equal amount of each sample as QC sample.Homo sapienshttps://www.ebi.ac.uk/metabolights/MTBLS15572Daya Zhang. Hainan medical university. 875025464@qq.com.The raw data were converted to the mzML format using ProteoWizardGroup875025464@qq.comPeople serum samples was maintained at -80°C until further testing.MetabolomicsMetabolomicsProteoWizard msconvertalcoholic liver diseaseAB SCIEX Triple Quad 6500+targeted analysisAgilent 1290 Infinity II UHPLCHomo sapienstargeted metabolite profilingserumAMPK signaling inhibitionMetabolomicsProteoWizard msconvertalcoholic liver diseaseAB SCIEX Triple Quad 6500+targeted analysisAgilent 1290 Infinity II UHPLCHomo sapienstargeted metabolite profilingserumAMPK signaling inhibitionAB Sciex Triple Quad 6500+ mass spectrometer was applied for assay development. Typical ion source parameters were as follows: IonSpray Voltage: +5000V/-4500V, Curtain Gas: 35 psi, Temperature: 400 ∘C, Ion Source Gas 1: 50 psi, Ion Source Gas 2: 50psi.3,4-Dihydroxyphenylacetic acidCaprolactam2'-O-MethyluridineOctanoic acidDecanoic Acid11S-hydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acidTetradecanedioateIndole-3-methyl acetateL-HistidineMalonaldehydeL-Leucine2-Hydroxy-4-(Methylthio)Butyric Acid3',5'-cyclic AMPIminodiacetic acidPhenylalanyl-GlutamateN-lactoyl-phenylalanineLauroylcarnitineUrea1-MethylxanthineRibonic acidOctadecanedioic acid2-MethylbutyroylcarnitineHyocholic acidAndrostendioneN1-AcetylspermidineN-Acetyl-LactosamineHexanoylcarnitineLauric acidEthyl glucuronideIndoxylsulfateArachidonoylcarnitinePyruvic acidButyrylcarnitine5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acidDocosapentaenoic acid(¡À)8-hydroxy-4Z,6E,10Z,13Z,16Z,19Z-docosahexaenoic acidOctanamideOleic acidGamma-Glutamyl-TyrosinePhenylalanyl-PhenylalanineGlutathione2-OxindoleSerotoninGlycochenodeoxycholic Acid-3-O-¦Â-glucuronide1,3-Dimethyluric-AcidN-(3-Acetamidopropyl)pyrrolidin-2-oneGlycochenodeoxycholic acid 3-Sulfate3-MethyldioxyindoleTestosteronePentaethylene glycolValyl-MethionineTiglylcarnitineDeoxycholic Acid-3-Sulfate5-Hydroxyhexanoic acidEicosapentaenoic acidValyl-IsoleucineGlycolithocholic Acid-3-SulfatePantothenic acidN-Acetyl-L-methionine3,3-Dimethylcyclohexanone3-Hydroxydecanoic acidUndecylenic AcidXanthurenic acidGlycocholic Acid-3-SulfateS-Adenosyl-homocysteineOleoylcarnitineOctanoylcarnitinePerillate3-Methylxanthine3-Epideoxycholic acid3-(3,4-Dimethoxyphenyl) Propionic AcidTetradecanoylcarnitine2-Aminooctanoic acid2-Hydroxyvaleric AcidLeucyl-Leucine(R)-6-oxopiperidine-2-carboxylic acid2-Oxohexanoic acid3-Succinoylpyridine13S-hydroxy-9Z,11E-octadecadienoic acidPhenylalanyl-Alanine5-MethoxytryptamineSperminePregnenolone sulfate4-Methylsalicylic acidChenodeoxycholic acidAdipic acidIsoleucyl-SerineP-Cresol sulfateDephospho-CoA4-Acetamidobutyric acidAdrenic acidHippuric acidalpha-Linolenic acidPutrescineN8-AcetylspermidineNorcholic acidPhenylalanyl-TryptophanIsocitric acid5-HydroxyindoleGlycohyodeoxycholic acidUrsodeoxycholic Acid-3-SulfateEthanolaminehomoserine lactoneGlycoursodeoxycholic acidIndole-3-acetic acidLinoleic acidCortisoneIsoleucyl-LeucineRetinol (Vitamin A)Palmitoleic acid9R-hydroxy-5Z,7E,11Z,14Z-eicosatetraenoic acid1-Methyl-L-histidinePhenylpyruvic acid1-MethylinosineTauroursodeoxycholic Acid-3-SulfateTaurolithocholic Acid-3-SulfateN-Acetyl-L-phenylalanineMyristelaidic acidN3-MethyluridineTraumatic acidCholic acidDocosahexaenoic acidArachidonic acidbeta-Hydroxyisovaleric acidSphingosine3,5-Dihydroxybenzoic acid2-Hydroxydecanoate1-Methyl-HydantoinN-Acetyl-L-tyrosineCaffeineTaurocholic acidN-Acetyl-Muramic AcidNonanoic acidVanillylmandelic acidTaurochenodeoxycholic Acid-3-SulfateAscorbic AcidAcetaminophen2-Hydroxystearic acid15S-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acidNicotinamideTheophylline11beta-HydroxyandrostenedioneHexanoic acid6-HydroxymelatoninPiperineN6-CarbamoylthreonyladenosineTaurodeoxycholic Acid-3-Sulfate3-Hydroxyoctanoic acidPyridoxamineHydroxyphenyllactic acid2-Aminoheptanoic acid1-Methylpseudouridine2-Hydroxy-3-methylvaleric acid3-Methyl-2-oxovaleric acidCitric acid2'-O-methyl-5-methyluridinecis-11,14,17-eicosatrienoic acidDecanoylcarnitineMOPEG sulfateThreonyl-LeucineValerylcarnitineTheobromineTauroursodeoxycholic acid4-Methyl-2-oxopentanoic acid3-Methoxy-4-hydroxyphenylglycol sulfateGlycocholic acidL-IsoleucineChenodeoxycholic acid-3-¦Â-D-GlucuronidePentadecanoic AcidUrsodeoxycholic acidNopalineLeucyl-PhenylalanineUrobilin(¡À)13-hydroxy-4Z,7Z,10Z,14E,16Z,19Z-docosahexaenoic acidDimethylamineGlycoursodeoxycholic Acid-3-SulfateIsoursodeoxycholic acidIndole-3-carboxaldehydeLevodopa1-AcetylprolineCotinine3-Hydroxysebacic AcidIsobutyrylglycine2-Hydroxycaproic acid2-Hydroxy-3-methylbutyric acidPalmitoylcarnitineIndole-3-pyruvic acidGlycodeoxycholic Acid-3-SulfateProlyl-Hydroxyproline2-Hydroxy-2-methylbutyric acidIndole-3-butyric acidIndole-3-lactic acidTaurochenodeoxycholic acidPhenyl hydrogen sulfateBis(3-Aminopropyl)AmineN-Acetyl-L-tryptophan3-(4-Methoxyphenyl)propanoic acidThymolHydrocortisone4-Hydroxyphenylpyruvic acidMaleamic AcidDihydrothyminePalmitic AcidDehydroepiandrosterone SulfateAlpha-Hydroxyhippuric Acid2',4',6'-TrihydroxyacetophenoneSalicyluric acidO-AdipoylcarnitineImidazoleacetic acidThymineGlycochenodeoxycholic acidGlycodeoxycholic acid-3-O-¦Â-glucuronide1-Methyluric acidDeoxycholic acidN1-AcetylspermineGlycohyocholic acidGlycodeoxycholic acidfalseEnterotoxigenic Bacteroides fragilis exacerbates alcoholic liver disease progression through kynurenine mediated AMPK signaling inhibition and retinoic acid depletionAbstract Background & Aims: Alcoholic liver disease (ALD) pathogenesis involves gut microbiota dysbiosis, but specific pathobionts and mechanisms remain unclear. This study investigated the role of patient-derived enterotoxigenic Bacteroides fragilis (ETBF) in ALD progression and its underlying molecular mechanisms. Methods: We recruited 25 healthy controls (HC) and 49 ALD patients. Fecal and serum samples underwent metagenomic and metabolomic analyses. Mechanistic validation employed fecal microbiota transplantation (FMT), ETBF monocolonization, and metabolite interventions in ethanol-fed mice, complemented by in vitro studies. Results:ALD patients exhibited dysbiosis characterized by marked ETBF enrichment and depletion of SCFA-producing bacteria (Faecalibacterium prausnitzii, Fusicatenibacter saccharivorans). Fecal SCFAs were significantly decreased and inversely correlated with liver injury markers. Serum metabolomics identified 128 dysregulated metabolites, including elevated pro-inflammatory 9,10-DHOME and decreased hepatoprotective lysophosphatidylcholines. Metagenomic and metabolomic data achieved high diagnostic accuracy and predicted disease progression (AUC=0.89). FMT from ALC patients or ETBF monocolonization exacerbated alcohol-induced liver injury, steatosis, inflammation, and fibrosis in mice. Mechanistically, ETBF upregulated hepatic and colon IDO1 via inflammatory cytokines TNF-α, increasing stool and hepatic kynurenine levels. Kynurenine exerted dual hepatotoxic effects: (1) inhibiting AMPK phosphorylation in hepatocytes, promoting lipid accumulation; and (2) inducing CYP26A1, accelerating retinoic acid (RA) catabolism. RA deficiency derepressed PPARγ transcription, activating hepatic stellate cells and driving fibrogenesis. Exogenous kynurenine recapitulated these effects, while RA supplementation attenuated Lipid formation and fibrogenic in ALD mice. Exogenous Anti-TNF-α or Talarozole alleviates ETBF-induced Lipid formation and fibrogenic in ALD mice. Conclusions: ETBF is associated with ALD progression through IDO1/kynurenine/CYP26A1/RA/PPARγ cascade, representing a novel pathogenic mechanism and offering multiple therapeutic targets.2026-09-072026-09-07MTBLS15572