{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:24:11Z","timestamp":1791419051861,"version":"4.3.3"},"reference-count":72,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271925"],"award-info":[{"award-number":["82271925"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971790"],"award-info":[{"award-number":["81971790"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2024KY364"],"award-info":[{"award-number":["2024KY364"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Postgraduate Education Innovation Project of Shanxi","award":["82271925"],"award-info":[{"award-number":["82271925"]}]},{"name":"the Postgraduate Education Innovation Project of Shanxi","award":["81971790"],"award-info":[{"award-number":["81971790"]}]},{"name":"the Postgraduate Education Innovation Project of Shanxi","award":["2024KY364"],"award-info":[{"award-number":["2024KY364"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The incidence of fatal anaphylaxis is increasing, but there is still no recognized \u201cgolden standard\u201d for forensic diagnosis. Due to its non-specific symptoms, especially cardiovascular symptoms without cutaneous changes, it can easily be misdiagnosed as acute myocardial infarction. Here, we established rat models (n = 12) of fatal anaphylaxis (FA), acute myocardial infarction (AMI), and coronary atherosclerosis with anaphylaxis (CAA). The untargeted metabolomics of plasma and 16S rRNA sequencing of fecal matter was performed, and a random forest was used to identify potential biomarkers. Three metabolites (tryptophan, trans-3-indole acrylic acid, and imidazole acetic acid) and three microbial genera (g_Prevotellaceae_Ga6A1_group, g_UCG_008, and g_Eubacterium_hallii_group) were identified as potential biomarkers for distinguishing anaphylaxis and non-anaphylaxis. The classification model of plasma metabolites showed a much better discriminatory performance than that of microbial genus, serum IgE, and tryptase. The performance of the microbial genera was superior to the serum IgE but inferior to the serum tryptase. Forensic samples of fatal anaphylaxis and non-anaphylaxis deaths (n = 12) were collected for untargeted metabolomics detection. The results showed that among the three identified metabolic biomarkers, tryptophan has better stability in cadaveric blood samples. Its diagnostic performance (AUC = 87.1528) was superior to serum IgE and tryptase, making it more suitable as a postmortem biomarker of fatal anaphylaxis.<\/jats:p>","DOI":"10.3390\/ijms26136292","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"6292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Metabolomic and Gut Microbiome Profiles Reveal Postmortem Biomarkers of Fatal Anaphylaxis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5353-2949","authenticated-orcid":false,"given":"Yaqin","family":"Bai","sequence":"first","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030606, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanpeng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030606, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8028-8113","authenticated-orcid":false,"given":"Zheng","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030606, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030606, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030606, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangman","family":"Yao","sequence":"additional","affiliation":[{"name":"Health Humanities Research Center, Shanxi Medical University, Jinzhong 030606, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5934-4164","authenticated-orcid":false,"given":"Keming","family":"Yun","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030606, China"},{"name":"Key Laboratory of Forensic Toxicology of Ministry of Public Security, Jinzhong 030606, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cairong","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030606, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjie","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030606, China"},{"name":"Translational Medicine Center, Shanxi Medical University, Jinzhong 030606, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dribin, T.E., Muraro, A., Camargo, C.A., Turner, P.J., Wang, J., Roberts, G., Anagnostou, A., Halken, S., Liebermann, J., and Worm, M. (2025). Anaphylaxis Definition, Overview, and Clinical Support Tool: 2024 Consensus Report\u2014a GA2LEN project. J. Allergy Clin. Immunol.","DOI":"10.1016\/j.jaci.2025.01.021"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1249280","DOI":"10.3389\/falgy.2023.1249280","article-title":"Population-based incidence of all-cause anaphylaxis and its development over time: A systematic review and meta-analysis","volume":"4","author":"Jilma","year":"2023","journal-title":"Front. Allergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100904","DOI":"10.1016\/j.waojou.2024.100904","article-title":"Identifying patients at risk of anaphylaxis","volume":"17","author":"DuToit","year":"2024","journal-title":"World Allergy Organ. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1097\/ACI.0b013e328259c328","article-title":"Cardiovascular disease and anaphylaxis","volume":"7","author":"Mueller","year":"2007","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100472","DOI":"10.1016\/j.waojou.2020.100472","article-title":"World allergy organization anaphylaxis guidance 2020","volume":"13","author":"Cardona","year":"2020","journal-title":"World Allergy Organ. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.jaip.2017.06.031","article-title":"Fatal Anaphylaxis: Mortality Rate and Risk Factors","volume":"5","author":"Turner","year":"2017","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.jaci.2020.01.017","article-title":"Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis","volume":"145","author":"Shaker","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/PAF.0000000000000972","article-title":"Association Between Cardiovascular Disease and Death by Anaphylaxis: A 20-Year Retrospective Study in Queensland, Australia","volume":"46","author":"Garland","year":"2024","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e28049","DOI":"10.1016\/j.heliyon.2024.e28049","article-title":"Anaphylactic deaths: A retrospective study of forensic autopsy cases from 2009 to 2019 in Shanghai, China","volume":"10","author":"Li","year":"2024","journal-title":"Heliyon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s12024-019-00134-1","article-title":"Medical and pathologic characteristics of fatal anaphylaxis: A Spanish nationwide 17-year series","volume":"15","year":"2019","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S1081-1206(10)60714-4","article-title":"Fatal anaphylaxis: Postmortem findings and associated comorbid diseases","volume":"98","author":"Greenberger","year":"2007","journal-title":"Ann. Allergy Asthma Immunol. Off. Publ. Am. Coll. Allergy Asthma Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1111\/cea.12748","article-title":"Increases in anaphylaxis fatalities in Australia from 1997 to 2013","volume":"46","author":"Mullins","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102610","DOI":"10.1016\/j.legalmed.2025.102610","article-title":"Utility of biomarkers in the postmortem diagnosis of fatal Anaphylaxis: A scoping review","volume":"74","author":"Karthikeyan","year":"2025","journal-title":"Leg. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101930","DOI":"10.1016\/j.legalmed.2021.101930","article-title":"Significance of detecting postmortem serum IgE in frozen corpses for the diagnosis of anaphylaxis in forensic","volume":"53","author":"Zheng","year":"2021","journal-title":"Leg. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/PAF.0000000000000572","article-title":"Reliable Postmortem Molecular Diagnosis of Anaphylaxis: Co-localization of Mast Cell Degranulation and Immunoglobulin E in Allergic Throat Tissues","volume":"41","author":"Wang","year":"2020","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"O\u0161tri\u0107 Pavlovi\u0107, I., Radovi\u0107, S., Krtini\u0107, D., Spiri\u0107, J., Kusi\u0107, N., Veli\u010dkovi\u0107, A., and Tomi\u0107-Spiri\u0107, V. (2024). Tryptase: The Silent Witness of Past and Ongoing Systemic Events. Medicina, 60.","DOI":"10.3390\/medicina60091380"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jflm.2018.12.006","article-title":"Postmortem IgE determination in coronary artery disease","volume":"62","author":"Lambert","year":"2019","journal-title":"J. Forensic Leg. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.jaci.2012.06.033","article-title":"Relation between objective measures of atopy and myocardial infarction in the United States","volume":"131","author":"Jaramillo","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1111\/1556-4029.13420","article-title":"Postmortem Serum Tryptase Levels with Special Regard to Acute Cardiac Deaths","volume":"62","author":"Xiao","year":"2017","journal-title":"J. Forensic Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jflm.2014.01.009","article-title":"Measurement of \u03b2-tryptase in postmortem serum in cardiac deaths","volume":"23","author":"Palmiere","year":"2014","journal-title":"J. Forensic Leg. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1111\/cea.13991","article-title":"Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers","volume":"51","author":"Obeso","year":"2021","journal-title":"Clin. Exp. Allergy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.jep.2018.07.013","article-title":"Deciphering biochemical basis of Qingkailing injection-induced anaphylaxis in a rat model by time-dependent metabolomic profiling based on metabolite polarity-oriented analysis","volume":"225","author":"Gao","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1328212","DOI":"10.3389\/fimmu.2024.1328212","article-title":"A systematic review and meta-analysis of proteomic and metabolomic alterations in anaphylaxis reactions","volume":"15","author":"Gallizzi","year":"2024","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.jacc.2016.06.044","article-title":"Comprehensive Metabolomic Characterization of Coronary Artery Diseases","volume":"68","author":"Fan","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1021\/acsomega.0c05178","article-title":"The Use of Gas Chromatography Coupled with High-Resolution Mass Spectrometry-Based Untargeted Metabolomics to Discover Metabolic Changes and Help in the Determination of Complex Causes of Death: A Preliminary Study","volume":"6","author":"Zhang","year":"2021","journal-title":"ACS Omega"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/imm.12930","article-title":"Immune regulation by microbiome metabolites","volume":"154","author":"Kim","year":"2018","journal-title":"Immunology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/j.jaci.2023.08.012","article-title":"Longitudinal dynamics of the gut microbiome and metabolome in peanut allergy development","volume":"152","author":"Chun","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2147\/JAA.S334752","article-title":"The Multiomics Analyses of Gut Microbiota, Urine Metabolome and Plasma Proteome Revealed Significant Changes in Allergy Featured with Indole Derivatives of Tryptophan","volume":"15","author":"Zhen","year":"2022","journal-title":"J. Asthma Allergy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e141935","DOI":"10.1172\/JCI141935","article-title":"Fecal microbiome and metabolome differ in healthy and food-allergic twins","volume":"131","author":"Bao","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40168-019-0683-9","article-title":"Alterations in the gut microbiome and metabolism with coronary artery disease severity","volume":"7","author":"Liu","year":"2019","journal-title":"Microbiome"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jare.2022.06.008","article-title":"Gut microbiota combined with metabolites reveals unique features of acute myocardial infarction patients different from stable coronary artery disease","volume":"46","author":"Dong","year":"2023","journal-title":"J. Adv. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jaci.2019.01.043","article-title":"High dietary fat intake induces a microbiota signature that promotes food allergy","volume":"144","author":"Hussain","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"121947","DOI":"10.1016\/j.lfs.2023.121947","article-title":"Importance of gut microbiota metabolites in the development of cardiovascular diseases (CVD)","volume":"329","author":"Hemmati","year":"2023","journal-title":"Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Al-Salam, S., Aburawi, E.H., Al-Hammadi, S., Dhanasekaran, S., Shafiuallah, M., Yasin, J., Sudhadevi, M., Awwad, A., Alper, S., and Kazzam, E. (2019). Cellular and Immunohistochemical Changes in Anaphylactic Shock Induced in the Ovalbumin-Sensitized Wistar Rat Model. Biomolecules, 9.","DOI":"10.3390\/biom9030101"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.atherosclerosis.2016.05.020","article-title":"Serum IgE levels are associated with coronary artery disease severity","volume":"251","author":"Guo","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mallavia, B., Oguiza, A., Lopez-Franco, O., Recio, C., Ortiz-Mu\u00f1oz, G., Lazaro, I., Lopez-Parra, V., Egido, J., and Gomez-Guerrero, C. (2013). Gene Deficiency in Activating Fc\u03b3 Receptors Influences the Macrophage Phenotypic Balance and Reduces Atherosclerosis in Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066754"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1161\/CIRCULATIONAHA.118.038534","article-title":"Germinal Center-Derived Antibodies Promote Atherosclerosis Plaque Size and Stability","volume":"139","author":"Centa","year":"2019","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/all.13481","article-title":"IgG1(+) B-cell immunity predates IgE responses in epicutaneous sensitization to foods","volume":"74","author":"Ellenbogen","year":"2019","journal-title":"Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1126\/scitranslmed.aat1479","article-title":"An IgG-induced neutrophil activation pathway contributes to human drug-induced anaphylaxis","volume":"11","author":"Chaisemartin","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1111\/all.15426","article-title":"The impact of type 2 immunity and allergic diseases in atherosclerosis","volume":"77","author":"Obeso","year":"2022","journal-title":"Allergy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.jaci.2010.01.056","article-title":"Activation of human mast cells through the platelet-activating factor receptor","volume":"125","author":"Kajiwara","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1053\/meta.2002.35196","article-title":"Effect of diet-induced obesity on ovalbumin-specific immune response in a murine asthma model","volume":"51","author":"Mito","year":"2002","journal-title":"Metab. Clin. Exp."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1111\/cea.13454","article-title":"Short-term high-fat diet feeding protects from the development of experimental allergic asthma in mice","volume":"49","author":"Wiese","year":"2019","journal-title":"Clin. Exp. Allergy"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/BF01541317","article-title":"Role of nitric oxide in anaphylactic shock","volume":"15","author":"Mitsuhata","year":"1995","journal-title":"J. Clin. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jaci.2024.02.023","article-title":"Metabolomics identifies phenotypic biomarkers of amino acid metabolism in milk allergy and sensitized tolerance","volume":"154","author":"Zhang","year":"2024","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"23534","DOI":"10.1038\/s41598-024-74623-x","article-title":"Serum metabolomics analysis reveals potential biomarkers of penicillins-induced fatal anaphylactic shock in rats","volume":"14","author":"Shi","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1038\/s12276-020-00504-8","article-title":"Glutamine reliance in cell metabolism","volume":"52","author":"Yoo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/jcb.240530412","article-title":"Exogenous glutamine requirement is confined to late events of T cell activation","volume":"53","author":"Spagnoli","year":"1993","journal-title":"J. Cell. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.immuni.2017.03.019","article-title":"Glutathione Primes T Cell Metabolism for Inflammation","volume":"46","author":"Mak","year":"2017","journal-title":"Immunity"},{"key":"ref_50","first-page":"224","article-title":"Metabolomics analysis of anaphylactoid reaction reveals its mechanism in a rat model","volume":"35","author":"Xu","year":"2017","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.atherosclerosis.2019.11.018","article-title":"Dietary linoleic acid and human health: Focus on cardiovascular and cardiometabolic effects","volume":"292","author":"Marangoni","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s12944-022-01765-0","article-title":"Metabolic pathway analysis of hyperuricaemia patients with hyperlipidaemia based on high-throughput mass spectrometry: A case\u2013Control study","volume":"21","author":"Wei","year":"2022","journal-title":"Lipids Health Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"106557","DOI":"10.1016\/j.intimp.2020.106557","article-title":"Gut microbiome alterations in patients with wheat-dependent exercise-induced anaphylaxis","volume":"84","author":"Du","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4354","DOI":"10.1039\/D3FO00195D","article-title":"A comparative study on the allergenic potential of \u03b2-lactoglobulin conjugated to glucose, caffeic acid and caffeoyl glucopyranose","volume":"14","author":"Wang","year":"2023","journal-title":"Food Funct."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e035871","DOI":"10.1136\/bmjopen-2019-035871","article-title":"Study protocol of a multicentre, randomised, controlled trial evaluating the effectiveness of probiotic and peanut oral immunotherapy (PPOIT) in inducing desensitisation or tolerance in children with peanut allergy compared with oral immunotherapy (OIT) alone and with placebo (the PPOIT-003 study)","volume":"10","author":"Loke","year":"2020","journal-title":"BMJ Open"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1016\/j.jaci.2017.11.053","article-title":"Basophils from allergic patients are neither hyperresponsive to activation signals nor hyporesponsive to inhibition signals","volume":"142","author":"Cassard","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1046\/j.0954-7894.2002.01354.x","article-title":"Lactobacillus casei strain Shirota suppresses serum immunoglobulin E and immunoglobulin G1 responses and systemic anaphylaxis in a food allergy model","volume":"32","author":"Shida","year":"2002","journal-title":"Clin. Exp. Allergy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.4014\/jmb.1306.06047","article-title":"Effect of orally administered Lactobacillus brevis HY7401 in a food allergy mouse model","volume":"23","author":"Lee","year":"2013","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.3168\/jds.2018-15683","article-title":"Effect of 3 lactobacilli on immunoregulation and intestinal microbiota in a \u03b2-lactoglobulin-induced allergic mouse model","volume":"102","author":"Fu","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"575","DOI":"10.4168\/aair.2018.10.6.575","article-title":"Probiotics as a Potential Immunomodulating Pharmabiotics in Allergic Diseases: Current Status and Future Prospects","volume":"10","author":"Sharma","year":"2018","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3389\/fimmu.2019.00191","article-title":"Gut Microbiome as Target for Innovative Strategies Against Food Allergy","volume":"10","author":"Paparo","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Lee, J., Lee, S.H., Gu, G.J., Choi, J.H., Jeong, K.T., Lee, J.K., and Kim, S.H. (2021). Alterations of lung microbial communities in obese allergic asthma and metabolic potential. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0256848"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1111\/all.16005","article-title":"Integrated gut metabolome and microbiome fingerprinting reveals that dysbiosis precedes allergic inflammation in IgE-mediated pediatric cow\u2019s milk allergy","volume":"79","author":"Plekhova","year":"2024","journal-title":"Allergy"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.1039\/D3FO05300H","article-title":"Oral administration of egg ovalbumin allergen induces dysregulation of tryptophan metabolism in sensitized BALB\/c mice","volume":"15","author":"Wang","year":"2024","journal-title":"Food Funct."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Jo, J.K., Seo, S.H., Park, S.E., Kim, H.W., Kim, E.J., Kim, J.S., Pyo, J.Y., Cho, K.M., Kwon, S.J., and Park, D.H. (2021). Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice. Metabolites, 11.","DOI":"10.3390\/metabo11080482"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3945\/jn.112.166322","article-title":"Habitual dietary intake is associated with stool microbiota composition in monozygotic twins","volume":"143","author":"Maukonen","year":"2013","journal-title":"J. Nutr."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Chen, X., Wu, Y., Hu, Y., Zhang, Y., and Wang, S. (2020). Lactobacillus rhamnosus GG Reduces \u03b2-conglycinin-Allergy-Induced Apoptotic Cells by Regulating Bacteroides and Bile Secretion Pathway in Intestinal Contents of BALB\/c Mice. Nutrients, 13.","DOI":"10.3390\/nu13010055"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"132762","DOI":"10.1016\/j.foodchem.2022.132762","article-title":"Role of the dietary components in food allergy: A comprehensive review","volume":"386","author":"Yang","year":"2022","journal-title":"Food Chem."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Malesza, I.J., Malesza, M., Walkowiak, J., Mussin, N., Walkowiak, D., Aringazina, R., Bartkowiak-Wieczorek, J., and M\u0105dry, E. (2021). High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review. Cells, 10.","DOI":"10.3390\/cells10113164"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Shen, X., Wang, M., Zhang, X., He, M., Li, M., Cheng, G., Wan, C., and He, F. (2019). Dynamic construction of gut microbiota may influence allergic diseases of infants in Southwest China. BMC Microbiol., 19.","DOI":"10.1186\/s12866-019-1489-4"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wu, Y., Wang, Y., Liu, X., Jiang, L., Guli, A., Sailike, J., Sun, X., Abuduwaili, N., Tuoliuhan, H., and Maney, K. (2020). Ziziphora clinopodioides flavonoids based on network pharmacology attenuates atherosclerosis in rats induced by high-fat emulsion combined with vitamin D(3) by down-regulating VEGF\/AKT\/NF-\u03baB signaling pathway. Biomed. Pharmacother., 129.","DOI":"10.1016\/j.biopha.2020.110399"},{"key":"ref_72","first-page":"98","article-title":"Comparison and improvement of the methods for establishment of rat models of myocardial ischemia","volume":"27","author":"Zhang","year":"2017","journal-title":"Chin. J. Comp. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6292\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:01:27Z","timestamp":1760032887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,29]]},"references-count":72,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26136292"],"URL":"https:\/\/doi.org\/10.3390\/ijms26136292","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,29]]}}}