#METABOLOMICS WORKBENCH LiFive55_20250207_080250 DATATRACK_ID:5602 STUDY_ID:ST003719 ANALYSIS_ID:AN006100 PROJECT_ID:PR002308 VERSION 1 CREATED_ON February 12, 2025, 9:15 pm #PROJECT PR:PROJECT_TITLE Differential network analysis integrates pathway mapping to characterize dynamic PR:PROJECT_TITLE metabolic changes in the progression of diabetic complications PR:PROJECT_SUMMARY Onset and progression of diseases are often characterized by dynamic changes in PR:PROJECT_SUMMARY various metabolites. Monitoring these metabolic fluctuations is a central focus PR:PROJECT_SUMMARY within the field of disease metabolomics. This study introduces an integrative PR:PROJECT_SUMMARY analytical method that combines cross-comparative differential network analysis PR:PROJECT_SUMMARY with network mapping to delineate the dynamic changes of diabetes rats in the PR:PROJECT_SUMMARY fecal metabolome induced by high-fat diet and streptozotocin. Our results PR:PROJECT_SUMMARY indicate that the fecal metabolite network is significantly associated with the PR:PROJECT_SUMMARY development of diabetes, and 13 specific biomarkers are related to the PR:PROJECT_SUMMARY progression of diabetic complications, namely galactose, lactose, PR:PROJECT_SUMMARY guanidinoacetate, alanine, phenylalanine, acetoin, uridine, adenine, PR:PROJECT_SUMMARY hypoxanthine, acetone, trimethylamine oxide (TMAO), 1-methycotinamide and PR:PROJECT_SUMMARY nicotinate. Interestingly, the networks analysis also uncovered age-related PR:PROJECT_SUMMARY metabolites including branched chain amino acids (leucine, isoleucine, valine), PR:PROJECT_SUMMARY urocanate, tyrosine, lysine succinate, betaine and cytosine, which may PR:PROJECT_SUMMARY potentially promote the onset and progression of diabetes. Pathway analysis PR:PROJECT_SUMMARY revealed disruptions in amino acid metabolism, ketone body synthesis and PR:PROJECT_SUMMARY degradation, glycolysis/gluconeogenesis, galactose metabolism, nicotinamide PR:PROJECT_SUMMARY metabolism, and purine metabolism, along with alterations in signaling pathways PR:PROJECT_SUMMARY related to mineral absorption and neurotransmitter synaptic transmission. The PR:PROJECT_SUMMARY cross-comparison network analysis in conjunction with network mapping analysis PR:PROJECT_SUMMARY constitutes an effective method for exploring dynamic metabolic networks PR:PROJECT_SUMMARY implicated in diseases pathogenesis. PR:INSTITUTE Xiamen university PR:LAST_NAME Liu PR:FIRST_NAME Wuping PR:ADDRESS Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and PR:ADDRESS Magnetic Resonance, Xiamen University, Xiamen 361005, China PR:EMAIL 13424036867@163.com PR:PHONE +8613424036867 #STUDY ST:STUDY_TITLE Differential network analysis integrates pathway mapping to characterize dynamic ST:STUDY_TITLE metabolic changes in the progression of diabetic complications ST:STUDY_SUMMARY Onset and progression of diseases are often characterized by dynamic changes in ST:STUDY_SUMMARY various metabolites. Monitoring these metabolic fluctuations is a central focus ST:STUDY_SUMMARY within the field of disease metabolomics. This study introduces an integrative ST:STUDY_SUMMARY analytical method that combines cross-comparative differential network analysis ST:STUDY_SUMMARY with network mapping to delineate the dynamic changes of diabetes rats in the ST:STUDY_SUMMARY fecal metabolome induced by high-fat diet and streptozotocin. Our results ST:STUDY_SUMMARY indicate that the fecal metabolite network is significantly associated with the ST:STUDY_SUMMARY development of diabetes, and 13 specific biomarkers are related to the ST:STUDY_SUMMARY progression of diabetic complications, namely galactose, lactose, ST:STUDY_SUMMARY guanidinoacetate, alanine, phenylalanine, acetoin, uridine, adenine, ST:STUDY_SUMMARY hypoxanthine, acetone, trimethylamine oxide (TMAO), 1-methycotinamide and ST:STUDY_SUMMARY nicotinate. Interestingly, the networks analysis also uncovered age-related ST:STUDY_SUMMARY metabolites including branched chain amino acids (leucine, isoleucine, valine), ST:STUDY_SUMMARY urocanate, tyrosine, lysine succinate, betaine and cytosine, which may ST:STUDY_SUMMARY potentially promote the onset and progression of diabetes. Pathway analysis ST:STUDY_SUMMARY revealed disruptions in amino acid metabolism, ketone body synthesis and ST:STUDY_SUMMARY degradation, glycolysis/gluconeogenesis, galactose metabolism, nicotinamide ST:STUDY_SUMMARY metabolism, and purine metabolism, along with alterations in signaling pathways ST:STUDY_SUMMARY related to mineral absorption and neurotransmitter synaptic transmission. The ST:STUDY_SUMMARY cross-comparison network analysis in conjunction with network mapping analysis ST:STUDY_SUMMARY constitutes an effective method for exploring dynamic metabolic networks ST:STUDY_SUMMARY implicated in diseases pathogenesis. ST:INSTITUTE Xiamen university ST:LAST_NAME Liu ST:FIRST_NAME Wuping ST:ADDRESS Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and ST:ADDRESS Magnetic Resonance, Xiamen University, Xiamen 361005, China ST:EMAIL 13424036867@163.com ST:PHONE +8613424036867 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Rattus norvegicus SU:TAXONOMY_ID 10116 SU:GENDER Male #FACTORS #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS 1 S_1 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 2 S_2 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 3 S_3 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 4 S_4 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 5 S_5 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 6 S_6 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 7 S_7 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 8 S_8 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial8 SUBJECT_SAMPLE_FACTORS 9 S_9 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial9 SUBJECT_SAMPLE_FACTORS 10 S_10 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 11 S_11 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 12 S_12 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 13 S_13 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 14 S_14 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 15 S_15 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 16 S_16 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 17 S_17 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 18 S_18 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial8 SUBJECT_SAMPLE_FACTORS 19 S_19 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial9 SUBJECT_SAMPLE_FACTORS 20 S_20 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 21 S_21 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 22 S_22 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 23 S_23 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 24 S_24 Sample source:Feces | Stage:Initial | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 25 S_25 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 26 S_26 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 27 S_27 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 28 S_28 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial8 SUBJECT_SAMPLE_FACTORS 29 S_29 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial9 SUBJECT_SAMPLE_FACTORS 30 S_30 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 31 S_31 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 32 S_32 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 33 S_33 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 34 S_34 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 35 S_35 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 36 S_36 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 37 S_37 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 38 S_38 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial8 SUBJECT_SAMPLE_FACTORS 39 S_39 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial9 SUBJECT_SAMPLE_FACTORS 40 S_40 Sample source:Feces | Stage:Initial | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesInitial SUBJECT_SAMPLE_FACTORS 41 S_41 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity! SUBJECT_SAMPLE_FACTORS 42 S_42 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity" SUBJECT_SAMPLE_FACTORS 43 S_43 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity# SUBJECT_SAMPLE_FACTORS 44 S_44 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity$ SUBJECT_SAMPLE_FACTORS 45 S_45 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity% SUBJECT_SAMPLE_FACTORS 46 S_46 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity& SUBJECT_SAMPLE_FACTORS 47 S_47 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity' SUBJECT_SAMPLE_FACTORS 48 S_48 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity8 SUBJECT_SAMPLE_FACTORS 49 S_49 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity9 SUBJECT_SAMPLE_FACTORS 50 S_50 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity( SUBJECT_SAMPLE_FACTORS 51 S_51 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity) SUBJECT_SAMPLE_FACTORS 52 S_52 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity* SUBJECT_SAMPLE_FACTORS 53 S_53 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity+ SUBJECT_SAMPLE_FACTORS 54 S_54 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity, SUBJECT_SAMPLE_FACTORS 55 S_55 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity- SUBJECT_SAMPLE_FACTORS 56 S_56 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity. SUBJECT_SAMPLE_FACTORS 57 S_57 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity/ SUBJECT_SAMPLE_FACTORS 58 S_58 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity8 SUBJECT_SAMPLE_FACTORS 59 S_59 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity9 SUBJECT_SAMPLE_FACTORS 60 S_60 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity0 SUBJECT_SAMPLE_FACTORS 61 S_61 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity1 SUBJECT_SAMPLE_FACTORS 62 S_62 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity2 SUBJECT_SAMPLE_FACTORS 63 S_63 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity3 SUBJECT_SAMPLE_FACTORS 64 S_64 Sample source:Feces | Stage:Obesity | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesObesity4 SUBJECT_SAMPLE_FACTORS 65 S_65 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity5 SUBJECT_SAMPLE_FACTORS 66 S_66 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity6 SUBJECT_SAMPLE_FACTORS 67 S_67 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity7 SUBJECT_SAMPLE_FACTORS 68 S_68 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity8 SUBJECT_SAMPLE_FACTORS 69 S_69 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity9 SUBJECT_SAMPLE_FACTORS 70 S_70 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity8 SUBJECT_SAMPLE_FACTORS 71 S_71 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity9 SUBJECT_SAMPLE_FACTORS 72 S_72 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity: SUBJECT_SAMPLE_FACTORS 73 S_73 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity; SUBJECT_SAMPLE_FACTORS 74 S_74 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity< SUBJECT_SAMPLE_FACTORS 75 S_75 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity= SUBJECT_SAMPLE_FACTORS 76 S_76 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity> SUBJECT_SAMPLE_FACTORS 77 S_77 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity? SUBJECT_SAMPLE_FACTORS 78 S_78 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity8 SUBJECT_SAMPLE_FACTORS 79 S_79 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity9 SUBJECT_SAMPLE_FACTORS 80 S_80 Sample source:Feces | Stage:Obesity | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesObesity80 SUBJECT_SAMPLE_FACTORS 81 S_81 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM81 SUBJECT_SAMPLE_FACTORS 82 S_82 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM82 SUBJECT_SAMPLE_FACTORS 83 S_83 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM83 SUBJECT_SAMPLE_FACTORS 84 S_84 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM84 SUBJECT_SAMPLE_FACTORS 85 S_85 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM85 SUBJECT_SAMPLE_FACTORS 86 S_86 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM86 SUBJECT_SAMPLE_FACTORS 87 S_87 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM87 SUBJECT_SAMPLE_FACTORS 88 S_88 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM88 SUBJECT_SAMPLE_FACTORS 89 S_89 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM89 SUBJECT_SAMPLE_FACTORS 90 S_90 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM90 SUBJECT_SAMPLE_FACTORS 91 S_91 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM91 SUBJECT_SAMPLE_FACTORS 92 S_92 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM92 SUBJECT_SAMPLE_FACTORS 93 S_93 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM93 SUBJECT_SAMPLE_FACTORS 94 S_94 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM94 SUBJECT_SAMPLE_FACTORS 95 S_95 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM95 SUBJECT_SAMPLE_FACTORS 96 S_96 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM96 SUBJECT_SAMPLE_FACTORS 97 S_97 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM97 SUBJECT_SAMPLE_FACTORS 98 S_98 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM98 SUBJECT_SAMPLE_FACTORS 99 S_99 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM99 SUBJECT_SAMPLE_FACTORS 100 S_100 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDM@ SUBJECT_SAMPLE_FACTORS 101 S_101 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMA SUBJECT_SAMPLE_FACTORS 102 S_102 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMB SUBJECT_SAMPLE_FACTORS 103 S_103 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMC SUBJECT_SAMPLE_FACTORS 104 S_104 Sample source:Feces | Stage:DM | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMD SUBJECT_SAMPLE_FACTORS 105 S_105 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDME SUBJECT_SAMPLE_FACTORS 106 S_106 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMF SUBJECT_SAMPLE_FACTORS 107 S_107 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMG SUBJECT_SAMPLE_FACTORS 108 S_108 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDM8 SUBJECT_SAMPLE_FACTORS 109 S_109 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDM9 SUBJECT_SAMPLE_FACTORS 110 S_110 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMH SUBJECT_SAMPLE_FACTORS 111 S_111 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMI SUBJECT_SAMPLE_FACTORS 112 S_112 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMJ SUBJECT_SAMPLE_FACTORS 113 S_113 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMK SUBJECT_SAMPLE_FACTORS 114 S_114 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDML SUBJECT_SAMPLE_FACTORS 115 S_115 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMM SUBJECT_SAMPLE_FACTORS 116 S_116 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMN SUBJECT_SAMPLE_FACTORS 117 S_117 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMO SUBJECT_SAMPLE_FACTORS 118 S_118 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDM 8 SUBJECT_SAMPLE_FACTORS 119 S_119 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDM 9 SUBJECT_SAMPLE_FACTORS 120 S_120 Sample source:Feces | Stage:DM | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMP SUBJECT_SAMPLE_FACTORS 121 S_121 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMCQ SUBJECT_SAMPLE_FACTORS 122 S_122 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMCR SUBJECT_SAMPLE_FACTORS 123 S_123 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMCS SUBJECT_SAMPLE_FACTORS 124 S_124 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMCT SUBJECT_SAMPLE_FACTORS 125 S_125 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMCU SUBJECT_SAMPLE_FACTORS 126 S_126 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMCV SUBJECT_SAMPLE_FACTORS 127 S_127 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMCW SUBJECT_SAMPLE_FACTORS 128 S_128 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMC 8 SUBJECT_SAMPLE_FACTORS 129 S_129 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMC 9 SUBJECT_SAMPLE_FACTORS 130 S_130 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMCX SUBJECT_SAMPLE_FACTORS 131 S_131 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMCY SUBJECT_SAMPLE_FACTORS 132 S_132 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMCZ SUBJECT_SAMPLE_FACTORS 133 S_133 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMC[ SUBJECT_SAMPLE_FACTORS 134 S_134 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMC\ SUBJECT_SAMPLE_FACTORS 135 S_135 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMC] SUBJECT_SAMPLE_FACTORS 136 S_136 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMC^ SUBJECT_SAMPLE_FACTORS 137 S_137 Sample source:Feces | Stage:DMC | Treatment:Ms RAW_FILE_NAME(Raw file names)=FecesDMC_ SUBJECT_SAMPLE_FACTORS 138 S_138 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMC 8 SUBJECT_SAMPLE_FACTORS 139 S_139 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMC 9 SUBJECT_SAMPLE_FACTORS 140 S_140 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMC` SUBJECT_SAMPLE_FACTORS 141 S_141 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCa SUBJECT_SAMPLE_FACTORS 142 S_142 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCb SUBJECT_SAMPLE_FACTORS 143 S_143 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCc SUBJECT_SAMPLE_FACTORS 144 S_144 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCd SUBJECT_SAMPLE_FACTORS 145 S_145 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCe SUBJECT_SAMPLE_FACTORS 146 S_146 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCf SUBJECT_SAMPLE_FACTORS 147 S_147 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCg SUBJECT_SAMPLE_FACTORS 148 S_148 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMC 8 SUBJECT_SAMPLE_FACTORS 149 S_149 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMC 9 SUBJECT_SAMPLE_FACTORS 150 S_150 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCh SUBJECT_SAMPLE_FACTORS 151 S_151 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCi SUBJECT_SAMPLE_FACTORS 152 S_152 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCj SUBJECT_SAMPLE_FACTORS 153 S_153 Sample source:Feces | Stage:DMC | Treatment:Nd RAW_FILE_NAME(Raw file names)=FecesDMCk #COLLECTION CO:COLLECTION_SUMMARY Fecal samples were collected from 0, 6, 8, and 12 weeks of high-fat feeding CO:COLLECTION_SUMMARY rats. Feces were obtained by manual abdominal stroking of the rat to induce CO:COLLECTION_SUMMARY defecation, and rapidly frozen in liquid nitrogen and stored at -80 ºC. CO:SAMPLE_TYPE Feces CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY A mouse model of type 2 diabetes was established by feeding a high-fat diet and TR:TREATMENT_SUMMARY using streptozotocin. All mice were randomly divided into two groups: normal TR:TREATMENT_SUMMARY diet group (Nd, n=16) and high-fat diet model sample group (Ms, n=24). After 6 TR:TREATMENT_SUMMARY weeks of high-fat feeding, the Ms mice reached the obesity stage, and then under TR:TREATMENT_SUMMARY fasting conditions, the Nd group and Ms group mice were intraperitoneally TR:TREATMENT_SUMMARY injected with 30 mg/kg of sodium citrate buffer and 1% streptozotocin solution TR:TREATMENT_SUMMARY (dissolved in sterile sodium citrate buffer at 0.1 M pH 4.4), respectively. The TR:TREATMENT_SUMMARY administration of streptozotocin lasted for 7 days, followed by 1 week of TR:TREATMENT_SUMMARY continued high-fat feeding, at which point the Ms mice reached the diabetes TR:TREATMENT_SUMMARY mellitus (DM) stage. Subsequently, the Ms mice continued high-fat feeding for an TR:TREATMENT_SUMMARY additional 4 weeks to reach the stage of diabetes mellitus complications (DMC). TR:TREATMENT_SUMMARY The obesity stage and diabetes mellitus stage were assessed by body weight and TR:TREATMENT_SUMMARY blood glucose, while the stage of diabetes mellitus complications was determined TR:TREATMENT_SUMMARY by hematoxylin-eosin staining of the organs (Kidneys, liver, and heart). TR:TREATMENT_COMPOUND Streptozotocin #SAMPLEPREP SP:SAMPLEPREP_SUMMARY 300 mg of feces were mixed with 1 mL of ice-cold Phosphate Buffered Saline-D2O SP:SAMPLEPREP_SUMMARY (0.75 M, pH=7.4, containing 0.05% 3-(trimethylsilyl)propionic acid, sodium SP:SAMPLEPREP_SUMMARY salt). The samples were homogenized by vortex for 1 min and subjected to three SP:SAMPLEPREP_SUMMARY freeze-thaw cycles in liquid nitrogen. Subsequently, the mixtures were sonicated SP:SAMPLEPREP_SUMMARY for 1 min in ice water, oscillated for 30 s and stored on ice for an additional SP:SAMPLEPREP_SUMMARY 30 s, with this procedure repeated 10 times. After centrifugations at 13,000 g SP:SAMPLEPREP_SUMMARY at 4ºC for 15 min, 600 μL of the supernatants was transferrred into a 5 mm NMR SP:SAMPLEPREP_SUMMARY tube for NMR analysis. #ANALYSIS AN:ANALYSIS_TYPE NMR AN:ANALYSIS_PROTOCOL_FILE NMR_analysis_protocol.pdf #NMR NM:INSTRUMENT_NAME Bruker AVANCE III HD 850MHz NM:INSTRUMENT_TYPE FT-NMR NM:NMR_EXPERIMENT_TYPE 1D-1H NM:NMR_COMMENTS 1H-NMR spectra of fecal samples were acquired at 298 K on a Bruker Advance III NM:NMR_COMMENTS 850 MHz spectrometer (Bruker, Rheinstetten, Germany) equipped with a 5 mm TXI NM:NMR_COMMENTS probe using a CPMGPR1D pulse sequence. Acquisition parameters included a NM:NMR_COMMENTS spin-echo loop time (2nτ) of 70 ms, 32 K data points, a spectral width of 17 NM:NMR_COMMENTS KHz, an acquisition time of 1.93 s, a relaxation delay of 5 s and 64 scans. The NM:NMR_COMMENTS 90° pulse length for each sample was individually adjusted during acquisition. NM:SPECTROMETER_FREQUENCY 850MHz NM:CHEMICAL_SHIFT_REF_STD The metabolites_metadata.xlsx file identified the relevant metabolites in fecal NM:CHEMICAL_SHIFT_REF_STD NMR spectra by matching the ppm of standard metabolites from the HMDB database, NM:CHEMICAL_SHIFT_REF_STD which facilitates the subsequent assignment of metabolites and further analysis. NM:NMR_RESULTS_FILE untargeted_bin1.txt UNITS:ppm #END