Metabolite identification was performed by matching MS/MS spectra against reference databases, including the HMDB (http://www.hmdb.ca/), Metlin (https://metlin.scripps.edu/), and Majorbio databases. The raw LC-MS data were first processed using Progenesis QI (Waters Corporation, Milford, USA) software for baseline correction, peak detection, integration, retention time calibration, and peak alignment, generating a data matrix containing retention time, mass-to-charge ratio (m/z), and peak intensity. On this basis, the MS/MS spectra were further matched against the above three databases to achieve metabolite identification.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - negative - reverse-phase","Liquid Chromatography MS - positive - reverse-phase"],"chromatography_protocol":["The supernatant was analyzed via LC-MS using an ACQUITY UPLC HSS T3 column (100 × 2.1 mm, 1.8 μm). Mass spectrometry was conducted on Thermo UHPLC-Q Exactive HF-X with ESI in positive/negative modes. Key parameters: ion source (425 °C), sheath/aux gas (50/13 arb), spray voltage (±3500 V), full MS resolution (60000) and MS/MS resolution (7500). Data-dependent acquisition (DDA) covered 70-1050 m/z.
"],"publication":["Darutigenol alleviates colitis through Akkermansia muciniphila-driven intestinal proline synthesis."],"submitter_name":["Wenjing Li"],"submitter_affiliation":["Shenyang Pharmaceutical University"],"organism_part":["A. muciniphila culture"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["100 μL of A. muciniphila culture was homogenized in 400 μL methanol:water (4:1, v/v). After incubation at -10 °C, samples were homogenized (50 Hz, 6 min), vortexed (5 °C, 30 sec), and sonicated (40 kHz, 30 min). Protein precipitation was performed at -20 °C for 30 min, followed by centrifugation (13,000 ×g, 4 °C, 15 min). 20 µL of supernatant from each sample was pooled to prepare the quality control sample.
"],"organism":["Akkermansia muciniphila"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS15418"],"author":["Jingming Jia. Shenyang Pharmaceutical University. jiajingming@syphu.edu.cn.","Wenjing Li. Shenyang Pharmaceutical University. wenjingli1886762@163.com."],"data_transformation_protocol":["The raw LC-MS data were first processed using Progenesis QI software for baseline correction, peak detection, integration, retention time calibration, and peak alignment, generating a data matrix containing retention time, mass-to-charge ratio, and peak intensity. Subsequently, preprocessing was performed on the Majorbio Cloud Platform, which included variable filtering (retaining variables with >80% non-zero values in at least one sample group and imputing missing values with the minimum observed value), total sum normalization to correct for technical variations, removal of variables with relative standard deviation >30% in QC samples, and log10 transformation. The preprocessed data were then subjected to OPLS-DA analysis using the R package ropls (v1.6.2), and significantly differential metabolites were screened based on VIP >1 and t-test P <0.05. Finally, pathway annotation was performed against the KEGG database, and pathway enrichment analysis was conducted using Fisher's exact test with Benjamini–Hochberg (FDR) correction for multiple testing.
"],"study_factor":["Group"],"submitter_email":["wenjingli1886762@163.com"],"sample_collection_protocol":["Akkermansia muciniphila (AKK bacteria) was cultured in an appropriate medium for 10 hours, after which the bacterial suspension was collected. Subsequently, the suspension was centrifuged at 4°C at a specific speed (e.g., 8,000 × g) for 10 minutes to pellet the bacterial cells. After centrifugation, the supernatant was carefully aspirated and collected as the desired sample.
"],"omics_type":["Metabolomics"],"study_design":["Gut microbiota","Metabolomics","AB SCIEX QTRAP 6500+","A. muciniphila culture","colitis","Mouse cecal contents","untargeted analysis","LC-ESI-MS/MS (UHPLC-Qtrap)","Proline","A. muciniphila,","Akkermansia muciniphila","IDO1"],"curator_keywords":["Gut microbiota","Metabolomics","AB SCIEX QTRAP 6500+","A. muciniphila culture","colitis","Mouse cecal contents","untargeted analysis","LC-ESI-MS/MS (UHPLC-Qtrap)","Proline","A. muciniphila,","Akkermansia muciniphila","IDO1"],"mass_spectrometry_protocol":["Mass spectrometry was conducted on Thermo UHPLC-Q Exactive HF-X with ESI in positive/negative modes. Key parameters: ion source (425 °C), sheath/aux gas (50/13 arb), spray voltage (±3500 V), full MS resolution (60000) and MS/MS resolution (7500). Data-dependent acquisition (DDA) covered 70-1050 m/z.
"],"metabolite_name":["Phenylpyruvic acid","Taurine","L-Phenylalanine","Deoxyribose","Phenylacetylglutamine","2-Hydroxybenzaldehyde","Hydantoin-5-propionic acid","PE-NMe(18:0/18:2(9Z,12Z))","L-Homoserine","O-Acetylserine","Trans-Aconitic Acid","4-(Glutamylamino) butanoate","5-Aminovaleric Acid","Saccharopine","Adenosine 3'-monophosphate","L-Histidine","2-Aminoacrylic acid","PA(10:0/8:0)","D-Sorbitol","Pyridoxal","LysoPC(P-18:1(9Z)/0:0)","Norfloxacin","Porphobilinogen","3-Hydroxyanthranilic Acid","CDP-DG(18:0/18:1(11Z))","Alpha-Ketoisovaleric Acid","Enol-phenylpyruvate","Pheophorbide a","4-Imidazolone-5-propionic acid","Urocanic Acid","PE(15:0/14:0)","Validamycin A","Imidazoleacetic acid riboside","PS(20:5(5Z,8Z,11Z,14Z,17Z)/20:4(5Z,8Z,11Z,14Z))","Glucosamine","N2-Acetylornithine","Formyl-5-hydroxykynurenamine","L-Palmitoylcarnitine","2-Isopropylmalic Acid","Pantothenic Acid","Phthalic Acid","N-methyl-L-glutamic Acid","L-Asparagine","Tetrahydrodipicolinate","Ureidopropionic acid","5-Amino-2-oxopentanoic acid","6-Hydroxymelatonin","3',5'-Cyclic GMP","Phosphate","2-Keto-glutaramic acid","11-beta-Hydroxyandrosterone-3-glucuronide","PE-NMe(15:0/14:0)","D-Galactose","Creatinine","Isopropylmaleic acid","Myo-Inositol","Lithocholic acid glucuronide","4-Hydroxyphenylacetylglutamic acid","Xanthosine","5-Hydroxylysine","Galactinol","Pyridoxine","Pseudouridine","Xanthine","Pimelic acid","Pretyrosine","N-formimidoyl-glutamic acid","Linatine","2-Phenylacetamide","N-Acetyl-L-Glutamic Acid","P-Aminobenzoic acid","Palmitaldehyde","Ciprofloxacin","Farnesylcysteine","N-Acetylneuraminic acid","PE(14:0/14:0)","Dihydrobiopterin","2-Amino-3-Methylsuccinic Acid","Isocitric Acid","2-Aminomuconic acid semialdehyde","2-Hydroxybutyric Acid","Thymidine","Aspartic Acid","Sphingosine 1-phosphate","Pseudouridine 5'-phosphate","Urobilinogen","L-Glutamic Acid","Caprylic acid","Gluconic Acid","Oleandomycin","6-Lactoyltetrahydropterin","Octopine","4-Hydroxyphenylpyruvic Acid","Nepsilon-Acetyl-L-lysine","Citric Acid","Myristic Acid","4-Acetamidobutanoic acid","Beta-Tyrosine","PS(20:5(5Z,8Z,11Z,14Z,17Z)/18:4(6Z,9Z,12Z,15Z))","Glyceric Acid","5'-Guanylic Acid","PA(14:0/20:4(8Z,11Z,14Z,17Z))","Malic Acid","Glycochenodeoxycholic acid 3-glucuronide","L-2-Amino-4-methylenepentanedioic acid","Uridine-5'-Monophosphate","1-Pyrroline-5-carboxylic acid","3-Hydroxybenzoic Acid","Histamine","N-Acetyl-L-aspartic acid","Isocitrate","L-Glutamic acid 5-phosphate","Uridine","Streptomycin sulfate","Hydroxypropionic acid","Hypoxanthine","Gluconolactone","Pseudooxynicotine","Maleic Acid","2-Hydroxyglutarate","PE(15:0/14:1(9Z))","PE-NMe(18:0/18:1(9Z))","Imidazolepropionic acid","Epinephrine","D-Pantothenoyl-L-cysteine","L-Glutamic gamma-semialdehyde","Dethiobiotin","Adenine","Biocytin","2-Aminobenzoic Acid","Stercobilin","N2-Acetyl-L-ornithine","Nicotinuric acid","PA(8:0/10:0)","D-Mannose 6-Phosphate","Palmitoleic acid","Phenethylamine glucuronide","Fructosyl-lysine","Uric Acid","Inosine","Sulfate","(3R,5S)-1-pyrroline-3-hydroxy-5-carboxylic Acid"],"additional_accession":[]},"is_claimable":false,"name":"Darutigenol alleviates colitis through Akkermansia muciniphila-driven intestinal proline synthesis","description":"Background: Gut microbiota dysbiosis is a critical contributor to the pathogenesis and progression of inflammatory bowel disease (IBD). Darutigenol (DL), a natural compound has demonstrated significant anti-inflammatory activity, but its low oral bioavailability limits its application. However, the therapeutic potential of this compound in colitis and whether it acts through microbiota-dependent mechanisms remain to be further explored. Results: To identify the key gut microbial species and metabolites contributing to DL-mediated amelioration of DSS-induced colitis in mice, we conducted gut microbiota analysis, antibiotic intervention, and fecal microbiota transplantation (FMT). Furthermore, metabolomic and transcriptomic analyses, as well as the targeted administration of specific bacteria and metabolites were conducted to investigate the microbiota-dependent mechanisms through which DL mitigates the severity of murine colitis. The results demonstrated that DL ameliorates colitis by modulating the gut microbiota, particularly through enriching Akkermansia muciniphila (A. muciniphila) and promoting the biosynthesis of its key metabolite, proline. Interestingly, DL was found to promote the growth of A. muciniphila in the gut by targeting indoleamine 2,3-dioxygenase 1 (IDO1). Additionally, proline supplementation exhibited a relieving effect on murine colitis by downregulating the IL-17 signaling pathway and its downstream signaling pathway. Conclusions: In summary, our findings reveal a novel therapeutic axis in which DL alleviates colitis via IDO1 inhibition-driven A. muciniphila expansion and proline-mediated immunoregulation, offering mechanistic insights for microbiota-targeted interventions of IBD.","dates":{"publication":"2026-08-21","submission":"2026-08-21"},"accession":"MTBLS15418","cross_references":{"HMDB":["HMDB0001199","HMDB0000050;HMDB0247583;PW_C000034;MJDBOTE0000767","HMDB0013677;HMDB0303719;HMDB0004461;HMDB0013676;HMDB0304270;HMDB0001870;HMDB0006115;MJDBOTE0000832","HMDB0001257;PW_C000971","HMDB0002005;PW_C001342","HMDB0000710","HMDB0002273;PW_C001535","HMDB0003423;PW_C000500;HMDB0000641;MJDBOTE0000775","HMDB0003950","HMDB0010315;LMST05010040","HMDB0242640;HMDB0000648;LMSP07000001","HMDB0000271;PW_C000185;MJDBOTE0000363","HMDB0004186","HMDB0060631","HMDB0112326;PW_C060724;LMGP03010148","HMDB0012114","HMDB0030483","HMDB0003767","HMDB0116188;PW_C076524","HMDB0000262;PW_C000179;MJDBOTE0000713","HMDB0001080","HMDB0000162;HMDB0251528;PW_C000106;MJDBOTE0000527","HMDB0029894","HMDB0000148;HMDB0003339;HMDB0060475","HMDB0033463","HMDB0008873;PW_C004921;LMGP02010445","HMDB0256004;HMDB0035688","HMDB0001565","HMDB0258420;HMDB0006482","HMDB0008559;LMGP01012219;PW_C004607","HMDB0010383","HMDB0061864;LMFA01031043","HMDB0004610;LMSP01030001","HMDB0006482","HMDB0008133;LMGP01010932;PW_C004181","HMDB0010385","HMDB0116749;PW_C060734;LMGP03010158","HMDB0012353;LMGP03010193;PW_C007883","HMDB0003550","HMDB0113969;PW_C059986","HMDB0114155;PW_C060172","HMDB0112881;PW_C061323","HMDB0012230","HMDB0004437","HMDB0000725;MJDBOTE0000547","HMDB0012108","HMDB0036461","HMDB0032231","HMDB0114160;PW_C060177","HMDB0008067;HMDB0013424;HMDB0008126;HMDB0008100;HMDB0011305;HMDB0013426;HMDB0011239;HMDB0011272","HMDB0032538","HMDB0113914;PW_C059930","HMDB0008067;PW_C004116;LMGP01012146","HMDB0000073;PW_C000052;MJDBSJD0000070","HMDB0116710;PW_C057621","HMDB0010391","HMDB0008751","HMDB0010395","HMDB0060039","HMDB0002925;LMFA01030158;HMDB0247333","HMDB0010396","HMDB0010379;PW_C006388","HMDB0244120","HMDB0008984","HMDB0060442","HMDB0000269;LMSP01020001;HMDB0242634;PW_C000184","HMDB0000220;PW_C000145;HMDB0303203;LMFA01010001","HMDB0304268","HMDB0001238;PW_C000956","HMDB0000187;PW_C000120;MJDBOTE0001776","HMDB0002035;HMDB0003654;HMDB0030677;MJDBOTE0000719","HMDB0248021","HMDB0004157","HMDB0000900;LMST03010001;HMDB0242614","HMDB0000036;LMST05040001;PW_C000025;MJDBOTE0000483","HMDB0000512","HMDB0304012","HMDB0039635","HMDB0000819;PW_C000654","HMDB0008491;HMDB0008327;HMDB0008061;HMDB0008622;HMDB0011222;HMDB0008193;HMDB0008422;HMDB0008787;HMDB0008293;HMDB0008721;HMDB0008818;HMDB0008357;HMDB0011228;HMDB0008753;HMDB0008521;HMDB0008456;HMDB0008161;HMDB0007929;HMDB0011224;HMDB0008261;HMDB0008260;HMDB0008457;HMDB0008621;HMDB0008524;HMDB0008392;HMDB0008488;HMDB0008391;HMDB0008258;HMDB0008225;HMDB0008424;HMDB0007997;HMDB0008586;HMDB0008687;HMDB0011223;HMDB0008062;HMDB0011227;HMDB0008063;HMDB0008228;HMDB0008819;HMDB0008060;HMDB0008619;HMDB0007931;HMDB0008162;HMDB0007996;HMDB0007896;HMDB0008653;HMDB0008786;HMDB0008719;HMDB0008359;HMDB0008720;HMDB0008556;HMDB0008259;HMDB0008425;HMDB0008159;HMDB0008390;HMDB0011290;HMDB0011226;HMDB0007930;HMDB0008127;HMDB0008194;HMDB0008620;HMDB0008654;HMDB0008423;HMDB0008557;HMDB0011225;HMDB0007895;HMDB0007962;HMDB0008227;HMDB0008393;HMDB0008160;HMDB0008094;HMDB0008458;HMDB0000086;HMDB0008360;HMDB0008027;HMDB0008523;HMDB0008096;HMDB0008294;HMDB0007995;HMDB0008093;HMDB0007994;HMDB0008587;HMDB0008195;PW_C000059;HMDB0007963;HMDB0008489;HMDB0008718;HMDB0008455;HMDB0008785;HMDB0008555;HMDB0008326;HMDB0008095;HMDB0008490;HMDB0008291;HMDB0008820;HMDB0008226;HMDB0011221;HMDB0008030;HMDB0008685;HMDB0008292;HMDB0008784;HMDB0008588;HMDB0008817;HMDB0007928;HMDB0008128;HMDB0008325;HMDB0008589;HMDB0008358;HMDB0008554;HMDB0008652;MJDBOTE0000471","HMDB0012130","HMDB0116153;PW_C076489","HMDB0004185","HMDB0012267","HMDB0303320;PW_C000976;HMDB0001263","HMDB0029737;HMDB0000195;HMDB0000197;MJDBSJD0000088","HMDB0035924;HMDB0000738","HMDB0001173;PW_C000910","HMDB0000472;PW_C000358","HMDB0003581","HMDB0240687;LMFA01060168","HMDB0012815","HMDB0240650;MJDBOTE0001351","HMDB0036458","HMDB0255213","HMDB0249220;HMDB0000030","HMDB0001505","HMDB0000306;PW_C000210;MJDBOTE0000392","HMDB0011106","HMDB0001084","HMDB0242532;HMDB0001370","HMDB0012150","HMDB0012234","HMDB0304170","HMDB0002299","HMDB0252858;HMDB0000086","HMDB0000118;PW_C000074","HMDB0000209;PW_C000135","HMDB0000206","HMDB0059758","HMDB0012115","HMDB0000258;PW_C000177","HMDB0000191;PW_C000123","HMDB0060441","HMDB0031842;HMDB0003464;MJDBOTE0001114","HMDB0006556;PW_C002808","HMDB0002215","HMDB0000975;PW_C000776","HMDB0000856","HMDB0012249","HMDB0001161;PW_C000899","HMDB0001185;PW_C000921;MJDBOTE0000477","HMDB0002281;HMDB0304198;PW_C001541","HMDB0246298;HMDB0001432;MJDBOTE0000469","HMDB0001325;PW_C001022","HMDB0000070;HMDB0000716;MJDBOTE0000664","HMDB0002322;MJDBOTE0000688","HMDB0003543","HMDB0031411","HMDB0001866;PW_C001240","HMDB0112273;LMGP03010930;PW_C057077","HMDB0008889;LMGP02010106;LMGP02011274;PW_C004937","HMDB0008199;LMGP01011677;PW_C004247","HMDB0258493","HMDB0002641;HMDB0041592","HMDB0000288;MJDBOTE0000717","HMDB0003540","HMDB0003224;HMDB0245099","HMDB0304312;HMDB0001078","HMDB0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