{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:16:05Z","timestamp":1788419765710,"version":"build-2803163510"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare the differences in gut microbiota diversity and serological parameters between children with Kawasaki disease (KD) complicated by coronary artery lesions (CAL) and those without CAL, and their association and auxiliary diagnostic value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A retrospective study was conducted on 57 KD children with CAL (CAL group) and 102 KD children without CAL (control group) diagnosed and treated in our hospital from January 2022 to December 2023. The gut microbiota diversity (Ace index, Shannon index), serum inflammatory markers and CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      were compared between the two groups. Pearson correlation analysis was used to explore the association between gut microbiota and serological parameters. Logistic regression analysis was employed to identify independent influencing factors. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the indicators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with the control group, the levels of serum CRP, TNF-\u03b1, IFN-\u03b3, IL-2, IL-4, IL-6, IL-10, and CD4\n                      <jats:sup>+\/<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio in the CAL group were significantly elevated, while the Ace index (an \u03b1-diversity indicator reflecting gut microbiota species richness) was significantly decreased (\n                      <jats:italic>P &amp;lt; 0.05<\/jats:italic>\n                      ). Pearson correlation analysis showed that the Ace index was negatively correlated with serum CRP, TNF-\u03b1, IFN-\u03b3, IL-2, IL-4, IL-6, IL-10, and CD4\n                      <jats:sup>+\/<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio (\n                      <jats:italic>P &amp;lt; 0.05<\/jats:italic>\n                      ). Multivariate Logistic regression analysis (with variance inflation factor VIF&amp;lt;5 for all variables, indicating no significant multicollinearity) demonstrated that the Ace index, pro-inflammatory factors (CRP, TNF-\u03b1, IFN-\u03b3, IL-6, IL-4), CD4\n                      <jats:sup>+\/<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio and the anti-inflammatory cytokine IL-10 were independently associated with CAL (\n                      <jats:italic>P &amp;lt; 0.05<\/jats:italic>\n                      ). ROC curve analysis showed that the area under the curve (AUC) for the combined detection was 0.911 (95% CI: 0.860\u20130.962), with a specificity of 81.37% and a sensitivity of 87.72%, and the efficacy was superior to any single indicator.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The Ace index, pro-inflammatory factors (CRP, TNF-\u03b1, IFN-\u03b3, IL-6, IL-4), and CD4\n                      <jats:sup>+\/<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio and IL-10 were independently associated with CAL. The combined detection of the above indicators demonstrated good efficacy for KD complicated by CAL and might provide clinical reference for early identification of high-risk children.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1865661","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:45:19Z","timestamp":1788417919000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The correlation and auxiliary diagnostic value of gut microbiota and serological indicators with Kawasaki disease complicated by coronary artery lesions"],"prefix":"10.3389","volume":"16","author":[{"given":"Shanshan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Immunology and Rheumatology, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B34","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1186\/s12887-024-04966-x","article-title":"Comparison of early characteristics of multisystemic inflammatory syndrome and Kawasaki disease in children and the course of Kawasaki disease in the pandemic","volume":"24","author":"Alkan","year":"2024","journal-title":"BMC Pediatr."},{"key":"B10","doi-asserted-by":"publisher","first-page":"105137","DOI":"10.1016\/j.ebiom.2024.105137","article-title":"Alterations in the gut mycobiome with coronary artery disease severity","volume":"103","author":"An","year":"2024","journal-title":"EBioMedicine"},{"key":"B14","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12969-021-00566-6","article-title":"The occurrence of coronary artery lesions in Kawasaki disease based on C-reactive protein levels: a retrospective cohort study","volume":"19","author":"An","year":"2021","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.31083\/rcm26566","article-title":"Correlation analysis of gut microbiota derivatives with coronary artery disease severity and prognosis","volume":"26","author":"Bai","year":"2025","journal-title":"Rev. Cardiovasc. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1086\/323155","article-title":"CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease","volume":"184","author":"Brown","year":"2021","journal-title":"J. Infect. Dis."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1237670","article-title":"Current knowledge of TNF-\u03b1 monoclonal antibody infliximab in treating Kawasaki disease: a comprehensive review","volume":"14","author":"Chen","year":"2023","journal-title":"Front. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"239","DOI":"10.4070\/kcj.2010.40.5.239","article-title":"Predicting factors for refractory Kawasaki disease","volume":"40","author":"Do","year":"2020","journal-title":"Korean Circ. J."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00124","article-title":"The gut microbiota-host partnership as a potential driver of Kawasaki syndrome","volume":"7","author":"Esposito","year":"2019","journal-title":"Front. Pediatr."},{"key":"B47","doi-asserted-by":"publisher","first-page":"4615","DOI":"10.1007\/s10067-025-07687-3","article-title":"Investigating the causal role of the gut microbiome in Kawasaki disease: mediating effects of immune cells","volume":"44","author":"Fan","year":"2025","journal-title":"Clin. Rheumatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.critrevonc.2019.09.003","article-title":"Gut microbiota and cancer: how gut microbiota modulates activity, efficacy and toxicity of antitumoral therapy","volume":"143","author":"Gori","year":"2019","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1111\/all.12558","article-title":"Th17- and Treg-related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease","volume":"70","author":"Guo","year":"2015","journal-title":"Allergy"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1416185","article-title":"Metagenomic analysis demonstrates distinct changes in the gut microbiome of Kawasaki diseases children","volume":"15","author":"Han","year":"2024","journal-title":"Front. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2343","DOI":"10.1111\/jcmm.14195","article-title":"The role of intestinal microbiota in cardiovascular disease","volume":"23","author":"Jin","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e481","DOI":"10.1161\/cir.0000000000001295","article-title":"Update on diagnosis and management of Kawasaki disease: a scientific statement from the American Heart Association","volume":"150","author":"Jone","year":"2024","journal-title":"Circulation"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01616","article-title":"Our evolving understanding of Kawasaki disease pathogenesis: role of the gut microbiota","volume":"11","author":"Kaneko","year":"2020","journal-title":"Front. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1038\/s41556-023-01145-5","article-title":"Bacterial induction of B cell senescence promotes age-related changes in the gut microbiota","volume":"25","author":"Kawamoto","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241813948","article-title":"Diagnosis, progress, and treatment update of Kawasaki disease","volume":"24","author":"Kuo","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41575-019-0258-z","article-title":"Gut microbiota-derived metabolites as key actors in inflammatory bowel disease","volume":"17","author":"Lavelle","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.2147\/TCRM.S226624","article-title":"Unusual presentation of Kawasaki disease with gastrointestinal and renal manifestations","volume":"15","author":"Lazea","year":"2019","journal-title":"Ther. Clin. Risk Manag"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4084\/MJHID.2024.052","article-title":"Expression of oxidative stress and inflammatory indicators for coronary artery disease in Kawasaki disease","volume":"16","author":"Li","year":"2024","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1080\/08820139.2023.2201283","article-title":"Interleukin-35 enhances regulatory T cell function by potentially suppressing their transdifferentiation into a T helper 17-like phenotype in Kawasaki disease","volume":"52","author":"Li","year":"2023","journal-title":"Immunol. Invest"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-018-0303-4","article-title":"Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-\u03b3 as biomarkers for early recognition","volume":"17","author":"Li","year":"2019","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1161\/strokeaha.120.032953","article-title":"Kawasaki disease may increase the risk of subsequent cerebrovascular disease","volume":"53","author":"Lin","year":"2022","journal-title":"Stroke"},{"key":"B51","doi-asserted-by":"publisher","first-page":"10991","DOI":"10.2147\/jir.s479879","article-title":"Case series on the efficacy and safety of tocilizumab in IVIG-resistant Kawasaki disease: A retrospective analysis of five patients","volume":"17","author":"Ling","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1055\/s-0036-1597903","article-title":"The intriguing link between the intestinal microbiota and cardiovascular disease","volume":"43","author":"Lippi","year":"2017","journal-title":"Semin. Thromb. Hemost"},{"key":"B41","doi-asserted-by":"publisher","first-page":"100525","DOI":"10.1016\/j.bj.2022.03.010","article-title":"Assessment of vascular and endothelial function in Kawasaki disease","volume":"46","author":"Lo","year":"2023","journal-title":"Biomed. J."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/nu14204385","article-title":"Assessment of selected intestinal permeability markers in children with food allergy depending on the type and severity of clinical symptoms","volume":"14","author":"Niewiem","year":"2022","journal-title":"Nutrients"},{"key":"B32","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.rdc.2023.03.002","article-title":"Kawasaki disease and multisystem inflammatory syndrome in children: common inflammatory pathways of two distinct diseases","volume":"49","author":"Noval Rivas","year":"2023","journal-title":"Rheum Dis. Clin. North Am."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-020-00406-5","article-title":"Mechanism of HMGB1-RAGE in Kawasaki disease with coronary artery injury","volume":"25","author":"Qian","year":"2020","journal-title":"Eur. J. Med. Res."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.903570","article-title":"The gut microbiota (microbiome) in cardiovascular disease and its therapeutic regulation","volume":"12","author":"Rahman","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s11926-020-00941-4","article-title":"Kawasaki disease: an update","volume":"22","author":"Rife","year":"2020","journal-title":"Curr. Rheumatol. Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1007\/s00246-020-02501-0","article-title":"Implications of changing Z-score models for coronary artery dimensions in Kawasaki disease","volume":"42","author":"Robinson","year":"2021","journal-title":"Pediatr. Cardiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"251","DOI":"10.18176\/jiaci.0300","article-title":"Autoimmune aspects of Kawasaki disease","volume":"29","author":"Sakurai","year":"2019","journal-title":"J. Investig. Allergol Clin. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"407","DOI":"10.2147\/vhrm.s291762","article-title":"Kawasaki disease: pathology, risks, and management","volume":"18","author":"Seki","year":"2022","journal-title":"Vasc. Health Risk Manag"},{"key":"B7","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1542\/pir.2023-006051","article-title":"Kawasaki disease","volume":"45","author":"Selmek","year":"2024","journal-title":"Pediatr. Rev."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.9698","article-title":"Effects of changes on gut microbiota in children with acute Kawasaki disease","volume":"8","author":"Shen","year":"2020","journal-title":"PeerJ"},{"key":"B33","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.jped.2023.02.005","article-title":"Prediction of coronary artery lesions based on C-reactive protein levels in children with Kawasaki disease: a retrospective cohort study","volume":"99","author":"Shuai","year":"2023","journal-title":"J. Pediatr. (Rio J)"},{"key":"B50","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107642","article-title":"Interleukin-35 regulates peripheral T cell activity in patients with Kawasaki disease","volume":"96","author":"Sun","year":"2021","journal-title":"Int. Immunopharmacol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1496293","article-title":"Unraveling the gut: the pivotal role of intestinal mechanisms in Kawasaki disease pathogenesis","volume":"15","author":"Tao","year":"2024","journal-title":"Front. Immunol."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2023.105168","article-title":"Epstein-Barr virus downregulates the \u03b17 nicotinic acetylcholine receptor of CD8+ T lymphocytes might associate with coronary artery lesions in Kawasaki disease patients","volume":"25","author":"Tao","year":"2023","journal-title":"Microbes Infect."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1268453","article-title":"Dysbiosis of the gut microbiota as a susceptibility factor for Kawasaki disease","volume":"14","author":"Teramoto","year":"2023","journal-title":"Front. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/ped4.12341","article-title":"Advances in understanding Kawasaki disease-related immuno-inflammatory response and vascular endothelial dysfunction","volume":"6","author":"Wang","year":"2022","journal-title":"Pediatr. Investig."},{"key":"B39","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1007\/s12265-022-10286-1","article-title":"NLRP3 inflammasome: a novel insight into heart failure","volume":"16","author":"Wang","year":"2023","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1582638","article-title":"Kawasaki disease: insights into the roles of T cells","volume":"16","author":"Wang","year":"2025","journal-title":"Front. Immunol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1124118","article-title":"The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Immunol."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.2147\/jir.s603769","article-title":"Tocilizumab for the treatment of intravenous immunoglobulin-resistant Kawasaki disease in children: Two case reports and literature review","volume":"19","author":"Wu","year":"2026","journal-title":"J. Inflamm. Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12865-021-00407-x","article-title":"Activin a suppresses peripheral CD8+ T lymphocyte activity in acute-phase Kawasaki disease","volume":"22","author":"Wu","year":"2021","journal-title":"BMC Immunol."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1457687","article-title":"scRNA+TCR-seq reveals the pivotal role of dual receptor T lymphocytes in the pathogenesis of Kawasaki disease and during IVIG treatment","volume":"15","author":"Xu","year":"2024","journal-title":"Front. Immunol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1007\/s12016-025-09120-8","article-title":"Potential mechanisms and hypotheses for pathogenic microorganisms triggering Kawasaki disease","volume":"68","author":"Yu","year":"2025","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.15662","article-title":"Alteration of the oral and gut microbiota in patients with Kawasaki disease","volume":"11","author":"Zeng","year":"2023","journal-title":"PeerJ"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-021-00589-z","article-title":"Factors affecting the duration of coronary artery lesions in patients with the Kawasaki disease: a retrospective cohort study","volume":"19","author":"Zhang","year":"2021","journal-title":"Pediatr. Rheumatol. Online J."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1865661\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:45:20Z","timestamp":1788417920000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1865661\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":52,"alternative-id":["10.3389\/fcimb.2026.1865661"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1865661","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1865661"}}