{"database":"MetaboLights","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Tabular":["ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14989/m_MTBLS14989_LC-MS_alternating_reverse-phase_v2_maf.tsv","ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14989/m_MTBLS14989_LC-MS_alternating_hilic_v2_maf.tsv"],"Txt":["ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14989/s_MTBLS14989.txt","ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14989/i_Investigation.txt","ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14989/a_MTBLS14989_LC-MS_alternating_hilic-1.txt","ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14989/a_MTBLS14989_LC-MS_alternating_reverse-phase.txt"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"ftp_download_link":["ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14989"],"metabolite_identification_protocol":["<p>Metabolites were identified and quantified using the H650 targeted metabolomics panel. Targeted metabolite annotation was based on predefined MRM transitions, retention time, and reference information provided in the metabolite quantification table. Metabolite identifiers and annotations included metabolite names, KEGG identifiers, HMDB identifiers, chemical taxonomy, retention time, chromatographic column information, and MRM transition information where available. Only reproducibly measured metabolites passing QC criteria were included in downstream analysis.</p>"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - alternating - hilic","Liquid Chromatography MS - alternating - reverse-phase"],"chromatography_protocol":["<p>LC separation was performed using an Agilent 1290 Infinity LC UHPLC system. Analytes were separated using both HILIC/Amide and C18 chromatographic methods. For HILIC separation, a Waters ACQUITY UPLC BEH Amide column (1.7 μm, 2.1 mm × 100 mm) was used. The column temperature was set at 35°C, the flow rate was 0.3 mL/min, and the injection volume was 2 μL. Mobile phase A was 90% water with 2 mM ammonium formate and 10% acetonitrile, and mobile phase B was acetonitrile with 0.4% formic acid. The gradient was 85% B at 0–1 min, 80% B at 3–4 min, 70% B at 6 min, 50% B at 10–15.5 min, and 85% B at 15.6–23 min.</p><p><br></p><p>For C18 reverse-phase separation, a Waters ACQUITY UPLC BEH C18 column (1.7 μm, 2.1 mm × 100 mm) was used. The column temperature was set at 40°C, the flow rate was 0.4 mL/min, and the injection volume was 2 μL. Mobile phase A was water with 5 mM ammonium acetate, and mobile phase B was 99.5% acetonitrile. The gradient was 5% B at 0 min, 60% B at 5 min, 100% B at 11–13 min, and 5% B at 13.1–16 min. Samples were maintained at 4°C during the analytical sequence.</p>"],"publication":["Low-Protein Diet Enhances Anti-Tumor Immunity in Pancreatic Cancer through Microbiota-Derived Uridine Diphosphate-Galactose."],"submitter_name":["yueying chen"],"submitter_affiliation":["Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine"],"organism_part":["serum"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["<p>Metabolites were extracted from mouse serum samples by adding 400 μL of cold methanol/acetonitrile (1:1, v/v) extraction solvent containing stable-isotope internal standards. Samples were vortexed to precipitate proteins and extract metabolites, then centrifuged at 14,000 × g for 20 min at 4°C. The supernatants were collected and dried in a vacuum centrifuge. For LC-MS/MS analysis, dried extracts were re-dissolved in 100 μL acetonitrile/water (1:1, v/v), vortexed, and centrifuged at 14,000 × g for 15 min at 4°C. The supernatants were injected for LC-MS/MS analysis. Pooled QC samples were prepared and analyzed together with biological samples.</p>"],"organism":["Mus musculus"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS14989"],"author":["yueying chen. Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine. chenyueyingcyy@163.com.","Ling Dong. Fudan University. dong.ling@zs-hospital.sh.cn."],"data_transformation_protocol":["<p>MultiQuant or Analyst software was used for MRM peak extraction and quantitative data processing. Peak areas and the ratios of metabolite peak areas to internal standard peak areas were calculated. Quantitative values were obtained using standard curves where applicable. QC samples were processed together with biological samples, and metabolites with coefficient of variation (CV) less than 30% in QC samples were considered reproducibly measured. The processed data were sum-normalized and imported into SIMCA-P version 14.1 for multivariate statistical analysis, including PCA and OPLS-DA. Statistical significance was assessed using an unpaired Student's t-test, with p &lt; 0.05 considered significant.</p>"],"study_factor":["Diet"],"submitter_email":["chenyueyingcyy@163.com"],"sample_collection_protocol":["<p>Serum samples were collected from C57 mice in a pancreatic ductal adenocarcinoma study. Mice were assigned to two diet-intervention groups: control diet and low-protein diet (LPD). Samples were collected after dietary intervention and processed using the same workflow for all groups. Pooled quality control (QC) samples were prepared by mixing equal aliquots from study samples and were injected throughout the LC-MS/MS sequence to monitor analytical stability and repeatability. Samples were stored frozen before metabolite extraction and LC-MS/MS analysis.</p>"],"omics_type":["Metabolomics"],"study_design":["Metabolomics","AB SCIEX QTRAP 6500+","Mus musculus","targeted analysis","targeted metabolite profiling","diet","serum","QC sample","Agilent 1290 Infinity LC","experimental sample","pancreatic ductal adenocarcinoma"],"curator_keywords":["Metabolomics","AB SCIEX QTRAP 6500+","Mus musculus","targeted analysis","targeted metabolite profiling","diet","serum","QC sample","Agilent 1290 Infinity LC","experimental sample","pancreatic ductal adenocarcinoma"],"mass_spectrometry_protocol":["<p>Mass spectrometry was performed on an AB SCIEX QTRAP 6500+ mass spectrometer equipped with an electrospray ionization (ESI) source. Data were acquired in positive and negative ion switching mode using multiple reaction monitoring (MRM). The ESI source parameters were as follows: source temperature 580°C, Ion Source Gas1 (GS1) 45, Ion Source Gas2 (GS2) 60, Curtain Gas (CUR) 35, and IonSpray Voltage +4500 V or -4500 V in positive or negative mode, respectively. MRM transitions were used for targeted quantitative data acquisition.</p>"],"metabolite_name":["Taurine","3-Phosphoglycerate","Allantoin","Glucaric acid","O-Phosphoethanolamine","Adenosine-3',5'-cyclic monophosphate(cAMP)","Malonyl-L-carnitine","Mannose 6-phosphate","D-Ribose 5-phosphate","N-Acetylaspartylglutamic acid (NAAG)","Thiamine monophosphate","Inosine triphosphate(ITP)","Methionine","Citrulline","Ribonic acid","N-Acetylaspartic acid","Uridine 5'-diphosphate(UDP)","Glucosamine","Lactulose","trans-Aconitic acid","Carnosine","Glycine","3,4-Dihydroxymandelic acid","cis-4-Hydroxy-D-proline","Cystine","Ureidopropionic acid","N-Acetylglutamine","N-Formylglycine","3-Methoxytyrosine","Hordenine","Arginine","Guanosine monophosphate （GMP）","Cystathionine","Glycolic acid","meso-Tartaric acid","N-Acetylglutamic acid","Phenylalanine","Glucose 6-phosphate （G6P）","Uridine diphosphate-N-acetylglucosamine","5-Hydroxylysine","Alloisoleucine","4-Guanidinobutanoic acid","Inosine-monophosphate(IMP)","N-Acetylcadaverine","Beta-Alanine","N-Acetylmannosamine","Gamma-Aminobutyric acid","Glycerol 3-phosphate","Norleucine","Guanosine","Aminocaproic acid","Creatine","7-methylguanosine","2,3-Diaminopropionic acid","D-2-Hydroxyglutaric acid","Pantothenic acid(VB5)","Acetylglycine","Cytosine","Tyrosine","Adenosine diphosphate ribose(ADP-ribose)","Uridine diphosphategalactose(UDP-galactose)","Glycylvaline","Aminoadipic acid","2-Aminoisobutyric acid","Alpha-Hydroxyisobutyric acid","Uridine 5'-monophosphate(UMP)","Adenosine monophosphate （AMP）","2-Phosphoglyceric acid","Oxidized glutathione","Oxalic acid","Succinic acid","Cytidine monophosphate（CMP)","Hydroxypropionic acid","Hypoxanthine","D-Mannosamine","Ornithine","Homoserine","Vitamin B1","Malonic acid","Vitamin B2","2-Hydroxyadenine","Serine","Proline","Cysteic acid","Isocitric acid","gamma-Glutamyl-methionine","3-Hydroxymethylglutaric acid","Glutarylcarnitine","Aspartic acid","Diethanolamine","2-Hydroxybutyric acid","Ophthalmic acid","Isoleucine","p-Octopamine","Adenosine","Thymideine-monophosphate(dTMP)","Homocitrulline","5-Hydroxy-tryptophan","Adenine","Threonic acid","Uric acid","Oxoadipic acid","3-Dehydroshikimate","Adenosine-5'-triphosphate(ATP)","Acetylcarnitine","Alpha-aminobutyric acid","Protirelin","Argininosuccinic acid","Homocysteine","3-Hydroxybutyric acid","Dimethylglycine","Glutamine","Sucrose","2'-Deoxyadenosine 5'-monophosphate(dAMP)","N-Methyl-aspartic acid","5-Methylcytosine","Glycyl-glycine","α-Ketoglutaric acid","Quinolinic Acid","Histidinol","N6-Acetyllysine","Guanosine diphosphate(GDP)","4-Trimethylammoniobutanoic acid","Histidine","Beta-Glycerophosphoric acid","Phosphonoacetate","Anserine","Ureidosuccinic acid","3-Methylhistidine","Tyramine","Threonine","N-Acetylproline","Vanillylmandelic acid","Adenosine-5'-diphosphate(ADP)","Urocanic acid","Propionylcarnitine","Lysine","Ciliatine","AICAR","Nicotinamide","Glycerophosphocholine","Indoxyl-β-D-glucuronide","Glutamic acid","1-Aminocyclopropanecarboxylic acid","Trehalose","Hydroxyproline","Glycyltyrosine","myo-Inositol","Pyroglutamic acid","Glucose 1-phosphate","Kynurenine","Tyrosyl-Alanine","Creatinine","Alanine","1,3-Diaminopropane","Phosphoenolpyruvic acid","Citicoline","N-Acetylputrescine","Trimethylamine-N-oxide","Tryptophan","Pyridoxine","Adenosine 2',3'-cyclic phosphate","6-Phosphogluconic acid","Citric acid","S-Adenosylmethionine","Fructose 6-phosphate","Deoxyguanosine","Uridine diphosphate glucuronic acid","5-Aminopentanoic acid","N-methyl-glutamic acid","Valine","Choline","Asparagine","Erythronic acid","Galactose 1-phosphate","Lactate","O-Succinyhomoserine","Kyotorphin","Gama-glutamylalanine","Imidazole Propionate","Nicotinamide ribotide","Pipecolic acid","Itaconic acid","Uridine diphosphate-N-acetylgalactosamine","Methylmalonic acid","Betaine","gamma-Glutamyl-valine","Maleic acid","Dimethylamine","Malic acid","Asymmetric dimethylarginine","Gluconic acid","4-Acetamidobutanoic acid","Galactaric acid","Trimethyllysine","Uridine diphosphate glucose(UDP-glucose)","Phosphorylcholine","Cytidine","Carnitine","Histamine","2,6-Diaminopimelic acid","Galacturonic acid","Phosphoserine","N-Alpha-acetyllysine","Methionine sulfoxide","3-Hydroxyisovaleric acid","2-Methylcitric Acid","1-Methylhistidine","Leucine","Citramalic acid","N-Methylalanine","cis-Aconitic acid","N-Acetylasparagine","Tartaric acid","1-Methyladenosine","2'-Deoxyuridine 5'-phosphate(dUMP)","3-Methylhistamine","Sarcosine","Norvaline","N-Formyl-kynurenine"],"additional_accession":[]},"is_claimable":false,"name":"Low-Protein Diet Enhances Anti-Tumor Immunity in Pancreatic Cancer through Microbiota-Derived Uridine Diphosphate-Galactose","description":"Low-protein diets (LPD) have been linked to improved metabolic health, but their role in pancreatic ductal adenocarcinoma (PDAC) immunotherapy remains unclear. Here we show that an LPD suppresses PDAC progression in male mice by remodeling the gut microbiota and activating anti-tumor immunity. LPD promoted immune activation and drove an immunostimulatory tumor-associated macrophage (TAM) phenotype. Microbiota depletion abolished these anti-tumor effects, and fecal microbiota transplantation (FMT) from LPD-fed donors transferred the protective phenotype to recipient mice. Mechanistically, LPD enriched the commensal bacterium Blautia coccoides, which produced UDP-galactose that activated the macrophage P2Y14R/STAT1 axis, upregulating STAT1 expression and inducing an immunostimulatory phenotype. Combining LPD, B. coccoides, or UDP-galactose with anti-PD1 therapy improved survival beyond anti-PD1 alone. In patients with advanced PDAC, reduced fecal B. coccoides and serum UDP-galactose levels correlated with poor clinical outcomes. These findings establish that LPD reshapes the gut microbiota and its metabolites to enhance anti-tumor immunity via the UDP-galactose/P2Y14R/STAT1 axis, offering a potential dietary strategy to improve PDAC immunotherapy responses and survival.","dates":{"publication":"2026-07-09","submission":"2026-07-09"},"accession":"MTBLS14989","cross_references":{"HMDB":["HMDB0005066","HMDB0005065","HMDB0006469","HMDB0000848","HMDB0028830","HMDB0029562","HMDB0002013;C02862","HMDB0013128","HMDB0000688","HMDB0000756","HMDB0000791;C02838","HMDB0000651","HMDB0000653;C18043","HMDB0001972","HMDB0000259;C00780","HMDB0003164;C00852","HMDB0001987","HMDB0000036;C05122","HMDB0000022;C05587","HMDB0001856;C00230","HMDB0001065;C02735","HMDB0001015;C03145","HMDB0000407","HMDB0000881;C02470","HMDB0037115","HMDB0000755;C03672","HMDB0000752","HMDB0000866;C01657","HMDB0000448;C06104","HMDB0004461;C09815","HMDB0012275;C05332","HMDB0011745;C02712","HMDB0000397;C00196","HMDB0000500;C00156","HMDB0002107;C01606","HMDB0001889;C07130","HMDB0003320;C19837","HMDB0001238;C00978","HMDB0000714;C01586","HMDB0033731;C06413","HMDB0000205;C00166","HMDB0000821;C05598","HMDB0000303;C00398","HMDB0000842;C06325","HMDB0000484;C06672","HMDB0001173;C00170","HMDB0001964;C01481","HMDB0011718;C00633","HMDB0000555","HMDB0029739;C02693","HMDB0000440;C05593","HMDB0000030;C00120","HMDB0000669;C05852","HMDB0000826;C16537","HMDB0000671;C02043","HMDB0060412;C16614","HMDB0000779;C05607","HMDB0013713","HMDB0011756;C02710","HMDB0000512;C03519","HMDB0029737;C08493","HMDB0000715;C01717","HMDB0000893;C08278","HMDB0000197;C00954","HMDB0011635","HMDB0000784;C08261","HMDB0254199;C01727","HMDB0000962;C00248","HMDB0000764;C05629","HMDB0029738","HMDB0000792;C08277","HMDB0000543","HMDB0000063;C00735","HMDB0258742","HMDB0000932","HMDB0001547;C02140","HMDB0000015;C05488","HMDB0000917;C17644","HMDB0000637;C05466","HMDB0000708","HMDB0002059;C08317","HMDB0000391;C04643","HMDB0000415;C17726","HMDB0000138;C01921","HMDB0000811;C15515","HMDB0002639;C11301","HMDB0000502","HMDB0000951;C05465","HMDB0000518;C02528","HMDB0000946;C07880","HMDB0000686;C17662","HMDB0000760","HMDB0000467","HMDB0000896;C05463","HMDB0000664","HMDB0304944","HMDB0000364;C17727","HMDB0000619;C00695","HMDB0000631;C05464","HMDB0000722;C02592","HMDB0304947","HMDB0000626;C04483","HMDB0000733;C15517","HMDB0034297;C08365","HMDB0011567","HMDB0000717;C17658","HMDB0002536;C17661","HMDB0000638;C02679","HMDB0061706","HMDB0000761","HMDB0001999;C06428","HMDB0000806;C06424","HMDB0003073;C06426","HMDB0001388;C06427","HMDB0002100;C16512","HMDB0003229;C08362","HMDB0012328","HMDB0002183;C06429","HMDB0001043;C00219","HMDB0006270","HMDB0000673;C01595","HMDB0005048;C04056","HMDB0001976","HMDB0002925;C03242","HMDB0244373;C16522","HMDB0000220;C00249","HMDB0002226;C16527","HMDB0000207;C00712","HMDB0000573;C01712","HMDB0002080;C08363","HMDB0002259","HMDB0000827;C01530","HMDB0002231;C16526","HMDB0002068;C08316","HMDB0000824;C03017","HMDB0005768;C02993","HMDB0029098","HMDB0028853","HMDB0002095","HMDB0011733;C02037","HMDB0028854","HMDB0013130","HMDB0001406;C00153","HMDB0000289;C00366","HMDB0000239;C00314","HMDB0004366;C06199","HMDB0003331;C02494","HMDB0000034;C00147","HMDB0000157;C00262","HMDB0000050;C00212","HMDB0000064;C00300","HMDB0000562;C00791","HMDB0002894;C02376","HMDB0000754;C20827","HMDB0004825;C04227","HMDB0000630;C00380","HMDB0000244;C00255","HMDB0000462;C01551","HMDB0000008;C05984","HMDB0000729","HMDB0000085;C00330","HMDB0000089;C00475","HMDB0010319;C03033","HMDB0000159;C00079","HMDB0000929;C00078","HMDB0000190;C00186","HMDB0001129;C00645","HMDB0304122;C02637","HMDB0011616;C02353","HMDB0000011;C01089","HMDB0060080;C03958","HMDB0255145","HMDB0001434","HMDB0003911;C05145","HMDB0000684;C00328","HMDB0000301;C00785","HMDB0003681;C02946","HMDB0000133;C00387","HMDB0000687;C00123","HMDB0001645;C01933","HMDB0001200;C02700","HMDB0000026;C02642","HMDB0000557","HMDB0000172;C00407","HMDB0094701","HMDB0000176;C01384","HMDB0000210;C00864","HMDB0000696;C00073","HMDB0000043;C00719","HMDB0004437;C06772","HMDB0000058;C00575","HMDB0000115;C03547","HMDB0000700;C01013","HMDB0000532","HMDB0000097;C00114","HMDB0000943;C01620","HMDB0002064;C02714","HMDB0013716;C01799","HMDB0000087;C00543","HMDB0002271;C20522","HMDB0000201;C02571","HMDB0006029","HMDB0001861","HMDB0000472;C00643","HMDB0003431;C00860","HMDB0000883;C00183","HMDB0000158;C00082","HMDB0000092;C01026","HMDB0000251;C00245","HMDB0000267;C01879","HMDB0000235;C00378","HMDB0000716;C00408","HMDB0094692;C02721","HMDB0000162;C00148","HMDB0001514;C00329","HMDB0000870;C00388","HMDB0000925;C01104","HMDB0001906;C03665","HMDB0036458;C01234","HMDB0000613","HMDB0006028","HMDB0000271;C00213","HMDB0000001;C01152","HMDB0000725;C01157","HMDB0000056;C00099","HMDB0000161;C00041","HMDB0003464;C01035","HMDB0000867;C01685","HMDB0000062;C00318","HMDB0000167;C00188","HMDB0060460;C03440","HMDB0000719;C00263","HMDB0001161;C01181","HMDB0000123;C00037","HMDB0000479;C01152","HMDB0000641;C00064","HMDB0000355;C03761","HMDB0003355;C00431","HMDB0000177;C00135","HMDB0000208;C00026","HMDB0000112;C00334","HMDB0000187;C00065","HMDB0000168;C00152","HMDB0000446;C12989","HMDB0000211;C00137","HMDB0000679;C02427","HMDB0002393;C12269","HMDB0000625;C00257","HMDB0002092;C00490","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