#METABOLOMICS WORKBENCH Fightingkyb_2024_20240820_064258 DATATRACK_ID:5128 STUDY_ID:ST003425 ANALYSIS_ID:AN005624 PROJECT_ID:PR002117 VERSION 1 CREATED_ON August 21, 2024, 11:28 pm #PROJECT PR:PROJECT_TITLE A mouse protozoan boosts antigen-specific mucosal IgA responses in a specific PR:PROJECT_TITLE lipid metabolism- and signaling-dependent manner PR:PROJECT_SUMMARY IgA antibodies play an important role in mucosal immunity. However, there is PR:PROJECT_SUMMARY still no effective way to consistently boost mucosal IgA responses, and the PR:PROJECT_SUMMARY factors influencing these responses are not fully understood. We observed that PR:PROJECT_SUMMARY colonization with the murine intestinal symbiotic protozoan Tritrichomonas PR:PROJECT_SUMMARY musculis (T.mu) boosted antigen-specific mucosal IgA responses in wild-type PR:PROJECT_SUMMARY C57BL/6 mice. This enhancement was attributed to the accumulation of free PR:PROJECT_SUMMARY arachidonic acid (ARA) in the intestinal lumen, which served as a signal to PR:PROJECT_SUMMARY stimulate the production of antigen-specific mucosal IgA. When ARA was prevented PR:PROJECT_SUMMARY from undergoing its downstream metabolic transformation using the 5-lipoxygenase PR:PROJECT_SUMMARY inhibitor zileuton or by blocking its downstream biological signaling through PR:PROJECT_SUMMARY genetic deletion of the Leukotriene B4 receptor 1 (Blt1), the T.mu-mediated PR:PROJECT_SUMMARY enhancement of antigen-specific mucosal IgA production was suppressed. Moreover, PR:PROJECT_SUMMARY both T.mu transfer and dietary supplementation of ARA augmented the efficacy of PR:PROJECT_SUMMARY an oral vaccine against Salmonella infection, with this effect being dependent PR:PROJECT_SUMMARY on Blt1. Our findings elucidate a tripartite circuit linking nutrients from the PR:PROJECT_SUMMARY diet or intestinal microbiota, host lipid metabolism, and the mucosal humoral PR:PROJECT_SUMMARY immune response. PR:INSTITUTE Xuzhou medical university PR:LAST_NAME Kou PR:FIRST_NAME Yanbo PR:ADDRESS Tongshan road 209, Xuzhou, Jiangsu, 221004, China PR:EMAIL fightingkyb@163.com PR:PHONE +86-051683262123 #STUDY ST:STUDY_TITLE Targeted free fatty acids metabolomics studies on serum, cecal content, cecum ST:STUDY_TITLE tissue, chow diet, and T.mu cells. ST:STUDY_SUMMARY Serum, cecal content, cecum tissue samples of murine, chow diet, and T.mu cells ST:STUDY_SUMMARY were collected to perform the targeted free fatty acids metabolome analysis. The ST:STUDY_SUMMARY aim of this study was to verify that whether T.mu could release free PUFA ST:STUDY_SUMMARY (especially ARA) to the intestinal tract of its host by comparing the PUFA ST:STUDY_SUMMARY concentration in the freshly isolated T.mu cells, chow diet, cecal content and ST:STUDY_SUMMARY serum of the host (Mus musculus).Based on the result of this targeted free fatty ST:STUDY_SUMMARY acids metabolomics studies, we found that T.mu could release ARA to the ST:STUDY_SUMMARY intestinal tract of its host and increase the concentration of ARA in its host's ST:STUDY_SUMMARY intestinal tract. ST:INSTITUTE Xuzhou medical university ST:LAST_NAME Kou ST:FIRST_NAME Yanbo ST:ADDRESS Tongshan road 209, Xuzhou, Jiangsu, 221004, China ST:EMAIL fightingkyb@163.com ST:PHONE +86-051683262123 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:GENDER Not applicable #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 - T_mu Sample source:T_mu cells | Treatment:isolated from cecal content RAW_FILE_NAME(Raw file name)=T_mu.CDF SUBJECT_SAMPLE_FACTORS - Diet Sample source:chow diet | Treatment:ground to power RAW_FILE_NAME(Raw file name)=Diet.CDF SUBJECT_SAMPLE_FACTORS - Ctrl_serum Sample source:serum | Treatment:control RAW_FILE_NAME(Raw file name)=Ctrl_serum.CDF SUBJECT_SAMPLE_FACTORS - T_mu_serum Sample source:serum | Treatment:colonized with Tmu RAW_FILE_NAME(Raw file name)=Ctrl_serum.CDF SUBJECT_SAMPLE_FACTORS - Ctrl_cecum Sample source:cecum tissue | Treatment:control RAW_FILE_NAME(Raw file name)=Ctrl_serum.CDF SUBJECT_SAMPLE_FACTORS - T_mu_cecum Sample source:cecum tissue | Treatment:colonized with Tmu RAW_FILE_NAME(Raw file name)=Ctrl_serum.CDF SUBJECT_SAMPLE_FACTORS - Ctrl_content Sample source:cecal content | Treatment:control RAW_FILE_NAME(Raw file name)=Ctrl_serum.CDF SUBJECT_SAMPLE_FACTORS - T_mu_content Sample source:cecal content | Treatment:colonized with Tmu RAW_FILE_NAME(Raw file name)=Ctrl_serum.CDF #COLLECTION CO:COLLECTION_SUMMARY WT C57/BL6 mice were colonized with or without T.mu for 7 days, and the serum, CO:COLLECTION_SUMMARY cecum tissue, cecal content samples were collected on day 7. For T.mu cells CO:COLLECTION_SUMMARY sample, T.mu cells were isolated and counted from T.mu positive cecal content. CO:COLLECTION_SUMMARY Samples were washed with cold PBS and then flash-frozen in liquid nitrogen. CO:SAMPLE_TYPE Serum, cecum tissue, cecal content, T.mu cells, chow diet #TREATMENT TR:TREATMENT_SUMMARY WT C57/BL6 mice were colonized with or without T.mu for 7 days, and the serum, TR:TREATMENT_SUMMARY cecum tissue, cecal content samples were collected on day 7. For T.mu cells TR:TREATMENT_SUMMARY sample, T.mu cells were isolated and counted from T.mu positive cecal content. TR:TREATMENT_SUMMARY For diet sample, the chow diet power was used. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY The weighed cecal content, cecum tissue, serum, animal chow diet powder, or SP:SAMPLEPREP_SUMMARY enumerated T.mu cells were transferred into new 2 mL EP tubes followed SP:SAMPLEPREP_SUMMARY extraction with 500 μL extracting solution [Isopropanol : n-Hexane = 2:3 SP:SAMPLEPREP_SUMMARY (V:V)], including 0.2 mg/L internal standard). After homogenized in a ball mill SP:SAMPLEPREP_SUMMARY for 4 min at 40 Hz and a 5 min ultrasound treatment, the samples were SP:SAMPLEPREP_SUMMARY centrifuged 16200 × g for 15 min at 4 °C. Then the supernatants were SP:SAMPLEPREP_SUMMARY transferred into new 2 mL EP tubes followed with nitrogen blow dry. The dried SP:SAMPLEPREP_SUMMARY samples were resuspended in 500 μL of methanol: trimethylsilyl diazomethane SP:SAMPLEPREP_SUMMARY solution (1:2), after standing 30 min at room temperature, another nitrogen blow SP:SAMPLEPREP_SUMMARY dry was performed. Then, the samples were resuspended in 160 μL of n-hexane SP:SAMPLEPREP_SUMMARY followed with a centrifugation of 16200 × g for 1 min. Finally, the SP:SAMPLEPREP_SUMMARY supernatants were transferred into new vials for GC-MS analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY DB-FastFAME capillary column (90 m × 0.25 mm × 0.25 µm, Agilent Technologies) CH:CHROMATOGRAPHY_TYPE GC CH:INSTRUMENT_NAME Agilent 7890B CH:COLUMN_NAME Agilent DB-FastFAME capillary column (90 m × 0.25 mm × 0.25 um) CH:SOLVENT_A - CH:SOLVENT_B - CH:FLOW_GRADIENT - CH:FLOW_RATE - CH:COLUMN_TEMPERATURE 230 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Agilent 5977B MS:INSTRUMENT_TYPE Single quadrupole MS:MS_TYPE EI MS:ION_MODE POSITIVE MS:MS_COMMENTS Mass spectrometry data were acquired in Scan/SIM mode over an m/z range of MS:MS_COMMENTS 33-400 after a solvent delay of 7 minutes. Fatty acid methyl esters (FAMEs) were MS:MS_COMMENTS identified by comparing them to commercial FAME standards (ANPEL, Shanghai, MS:MS_COMMENTS China, Cat# CDAA-252). The absolute concentrations of FAMEs were calculated MS:MS_COMMENTS using calibration curves based on the internal standard method. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS μg/ml for serum, μg/g for cecal content, μg/g for diet, μg/8*10^7 T.mu cells MS_METABOLITE_DATA_START Samples T_mu_content Ctrl_content Ctrl_cecum T_mu_cecum Ctrl_serum T_mu_serum T_mu Diet Factors Sample source:cecal content | Treatment:colonized with Tmu Sample source:cecal content | Treatment:control Sample source:cecum tissue | Treatment:control Sample source:cecum tissue | Treatment:colonized with Tmu Sample source:serum | Treatment:control Sample source:serum | Treatment:colonized with Tmu Sample source:T_mu cells | Treatment:isolated from cecal content Sample source:chow diet | Treatment:ground to power Oleic acid 37627.95 56029.43 30279.12 60759.18 45231.54 32806.51 19580.48 466521.47 Palmitic Acid 75445.56 67998.47 34576.42 53400.25 80887 59882.24 95952.18 529736.32 Octanoic Acid 27.6 5.54 0 0 40.56 31.08 36.32 1835.27 Decanoic Acid 54.17 25.38 39.07 29.52 31.14 36.76 3506 49.82 Elaidic acid 0 0 0 0 81.73 41.62 4192.23 0 Lauric Acid 443.29 20.22 86.38 91.78 13.72 5.14 91.26 642.04 Linoleic acid 69682.13 69057.69 23288.7 50446.44 70355.06 64783.42 66078.22 1361381.6 Myristic Acid 2204.33 1819.72 650.5 1825.61 1181.47 599.61 1548.93 25005.82 Pentadecanoic Acid 3562.1 1144.14 451.22 686.58 434.63 281.83 4213.02 4075.64 Stearic Acid 66344.88 38976.5 29705.75 30269.88 35981.51 30912.09 45962 204561.27 Tridecylic Acid 237.73 28.09 4.66 34.19 0 0 36.8 152.76 Behenic Acid 8345.2 5311.53 393.16 609.45 632.88 345.05 2157.86 18918.39 Undecanoic Acid 0 0 6.01 0.23 0 0 12.18 13.12 all-cis-5,8,11,14-Eicosatetraenoic Acid 16445.13 3779.78 19633.23 21338.07 18269.15 16387.36 13631.63 6265.68 Tricosanoic Acid 1534.17 1214.7 71.96 63.71 0 0 288.27 1558.46 Linolenic acid 3233.24 4060.03 548.59 1734.04 2401.3 2538.86 3067.46 254061.25 all-cis-4,7,10,13,16-Docosapentaenoic Acid 195.99 93.67 516.03 503.7 548.96 438.07 282.89 0 all-cis-5,8,11,14,17-Eicosapentaenoic Acid 1057.51 521.05 959.08 778.96 1052.08 878.15 1197.67 24629.76 Myristoleic acid 1311.1 150.44 35.96 60.21 107.44 58.96 232.32 1000.81 Lignoceric Acid 6128.87 4398.34 314.45 362.33 59.37 45.42 708.52 5689.14 Erucic acid 2234.25 844.42 178.27 421.8 122.32 130.02 476.68 2279.46 cis-6-Octadecenoic acid 0 0 0 0 0 0 2976.87 0 all-cis-4,7,10,13,16,19-Docosahexaenoic Acid 6828.01 1291.61 6227.32 7617.97 17286.6 14454.94 6893.52 17846.87 Arachidic Acid 6570.67 5039.45 372.68 455.85 111.98 86.35 1320.62 11317 all-cis-7,10,13,16-Docosatetraenoic Acid 942.63 303.98 1978.27 2439.37 337.17 410.5 394.25 879.1 cis-11-Eicosenoic Acid 3492.32 2759.65 526.05 1602.77 1415.14 872.79 851.33 29203.73 Heptadecanoic Acid 2452.18 1665.55 893.6 855.64 803.85 630.46 2490.08 2642.19 Heneicosanoic Acid 1026.04 962.22 48.68 82.18 22.29 10.25 241.63 1065.95 15-Nervonic acid 2031.72 804.39 0 0 0 0 0 6152.66 cis,cis,cis-8,11,14-Linolenic Acid 2650.28 1001.68 2993.7 3405.89 4047.14 2135.56 1534.45 1163.22 gamma-Linolenic acid 205.71 134.08 238.15 383.13 725.47 917.38 84.89 1236.35 Palmitoleic acid 3071.94 3714.46 2444.58 8255.91 8680.01 3255.93 1491.37 62498.55 trans-11-Octadecenoic acid 49515.3 37244.25 1231.04 3722.62 283.07 41 48051.64 0 cis,cis-11,14-Eicosadienoic Acid 861.62 408.81 1005.83 1128.37 1084.43 561.85 296.75 3764.44 Linoelaidic acid 22.18 115.66 0 0 0 0 118.66 454.48 all-cis-7,10,13,16,19-Docosapentaenoic acid 461.11 234.58 1048.62 1224.34 917.42 674.85 257.9 3799.36 Palmitelaidic acid 0 0 67.69 1356.86 0 0 0 4794.52 cis-10-Heptadecenoic Acid 0 0 30.87 349.12 0 0 0 0 all-cis-11,14,17-Eicosatrienoic Acid 0 0 38.3 44.67 54.19 41 148.8 375.3 cis,cis-13,16-Docosadienoic Acid 0 0 0 0 0 0 0 85.38 Myristelaidic acid 0 0 0 0 0 0 0 170.45 cis-11-Octadecenoic acid 9206.95 6149.43 6730.93 9885.31 7274.64 3609.61 3059.87 96145.78 trans-10-Heptadecenoic acid 52.3 23.25 91.48 84.6 64.35 61.48 62.32 0 trans-13-Docosenoic acid 295.9 278.47 64.15 72.98 93.81 46.44 296.2 3967.64 6-Octadecenoic acid 0 0 0 0 0 0 0 0 cis-10-Pentadecenoic Acid 342.16 235.57 0 0 0 0 291.24 0 trans-10-pentadecenoic acid 0 0 0 0 0 0 0 0 trans-10-Nonadecenoic acid 401.22 444.27 0 0 62.2 79.64 295.49 0 trans-11-Eicosenoic acid 182.12 111.14 0 0 0 0 0 0 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name CAS Molecular weight KEGG ID Oleic acid 112-80-1 282.4614 C00712 Palmitic Acid 57-10-3 256.4241 C00249 Octanoic Acid 124-07-2 144.21 C06423 Decanoic Acid 334-48-5 172.26 C01571 Elaidic acid 112-79-8 282.4614 C01712 Lauric Acid 143-07-7 200.32 C02679 Linoleic acid 60-33-3 280.4455 C01595 Myristic Acid 544-63-8 228.37 C06424 Pentadecanoic Acid 1002-84-2 242.4 C16537 Stearic Acid 57-11-4 284.4772 C01530 Tridecylic Acid 638-53-9 214.34 C17076 Behenic Acid 112-85-6 340.5836 C08281 Undecanoic Acid 112-37-8 186.291 C17715 all-cis-5,8,11,14-Eicosatetraenoic Acid 506-32-1 304.4669 C00219 Tricosanoic Acid 2433-96-7 354.61 NA Linolenic acid 463-40-1 278.4296 C06427 all-cis-4,7,10,13,16-Docosapentaenoic Acid 25182-74-5 330.5 C16513 all-cis-5,8,11,14,17-Eicosapentaenoic Acid 10417-94-4 302.451 C06428 Myristoleic acid 544-64-9 226.355 C08322 Lignoceric Acid 557-59-5 368.6367 C08320 Erucic acid 112-86-7 338.5677 C08316 cis-6-Octadecenoic acid 593-39-5 282.4614 C08363 all-cis-4,7,10,13,16,19-Docosahexaenoic Acid 6217-54-5 328.4883 C06429 Arachidic Acid 506-30-9 312.5304 C06425 all-cis-7,10,13,16-Docosatetraenoic Acid 28874-58-0 332.52 C16527 cis-11-Eicosenoic Acid 5561-99-9 310.5145 C16526 Heptadecanoic Acid 506-12-7 270.45 NA Heneicosanoic Acid 2363-71-5 326.56 NA 15-Nervonic acid 506-37-6 366.6208 C08323 cis,cis,cis-8,11,14-Linolenic Acid 1783-84-2 306.4828 C03242 gamma-Linolenic acid 506-26-3 278.4296 C06426 Palmitoleic acid 373-49-9 254.4082 C08362 trans-11-Octadecenoic acid 693-72-1 282.4614 C08367 cis,cis-11,14-Eicosadienoic Acid 5598-38-9 308.4986 C16525 Linoelaidic acid 506-21-8 280.4455 NA all-cis-7,10,13,16,19-Docosapentaenoic acid 24880-45-3 330.5042 C16513 Palmitelaidic acid 10030-74-7 254.4082 NA cis-10-Heptadecenoic Acid 29743-97-3 268.4348 NA all-cis-11,14,17-Eicosatrienoic Acid 17046-59-2 306.4828 C16522 cis,cis-13,16-Docosadienoic Acid 17735-98-7 336.5518 C16533 Myristelaidic acid 50286-30-1 226.36 NA cis-11-Octadecenoic acid 506-17-2 282.46 C21944 trans-10-Heptadecenoic acid 126761-43-1 268.4348 NA trans-13-Docosenoic acid 506-33-2 338.57 NA 6-Octadecenoic acid 593-40-8 282.46 NA cis-10-Pentadecenoic Acid 84743-29-3 240.38 NA trans-10-pentadecenoic acid 321744-58-5 240.38 NA trans-10-Nonadecenoic acid 67228-95-9 296.5 NA trans-11-Eicosenoic acid 62322-84-3 310.51 NA METABOLITES_END #END