{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:08:47Z","timestamp":1789456127803,"version":"build-2803163510"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bronchial asthma is a highly heterogeneous chronic inflammatory airway disorder. Syndrome differentiation-guided Traditional Chinese Medicine (TCM) treatment for asthma delivers distinct advantages, including fewer adverse reactions and superior anti-inflammatory efficacy. Nevertheless, the intrinsic biological mechanisms underlying TCM asthma syndromes remain largely uncharacterized, restricting the objective and standardized differentiation of TCM subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated transcriptomic, proteomic, metabolomic and oral microbiome data from asthma patients and healthy controls to map asthma molecular and microbiome landscapes. Two representative TCM subtypes\u2014Phlegm-Dampness Obstructing the Lungs (PZLP) and Lung-Qi Deficiency (LQD)\u2014were stratified and compared via differential analysis, WGCNA, LEfSe and random forest machine learning to dissect shared asthma-related molecular features, subtype-specific molecular disparities and potential objective diagnostic biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Comprehensive multi-omics and oral microbiome comparisons revealed correlational molecular discrepancies between asthma patients and healthy individuals. Our omics data suggest that asthma-related molecular alterations are tightly associated with three core pathological cascades: dysregulated glycerophospholipid metabolism, potential excessive activation of the NF-\u03baB inflammatory signaling pathway, and impaired phagosome function. Beyond the universal disease-associated molecular signatures of asthma, prominent metabolic and inflammatory phenotypic divergences were detected between the two TCM subtypes. The PZLP subtype showed correlational omics signatures suggestive of elevated lipogenic activity, aberrant MAPK inflammatory pathway activation, and massive intracellular lipid accumulation. In contrast, the LQD subtype exhibited correlated downregulation of lipid transporter genes (e.g., ABCA13), which hypothetically implies compromised lipid transport capacity and disrupted cell membrane homeostasis. Oral microbiota profiling demonstrated profound structural remodeling in asthmatic patients. Although PZLP and LQD patients shared analogous overall microbial community structures, their microbial functional pathways diverged substantially: the LQD group was enriched in methane and glycerol metabolic pathways, whereas the PZLP group displayed overrepresentation of serotonergic and dopaminergic synaptic regulatory pathways. A diagnostic classification model built on differential microbial biomarkers achieved an area under the receiver operating characteristic curve (AUC) of 0.889, demonstrating robust discriminative capacity for distinguishing the two TCM syndromes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study delineates correlational immunometabolic and oral microbiome signatures of asthma and uncovers potential subtype-specific molecular and microbial markers for two classic TCM asthma patterns. These observations provide testable mechanistic hypotheses for interpreting the molecular pathogenesis of asthma and could supply a preliminary theoretical foundation for objective TCM syndrome differentiation, personalized intervention and targeted asthma therapeutic development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1922660","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:25:10Z","timestamp":1789453510000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From disease to syndrome pattern: a study on the differentiation of traditional Chinese medicine syndrome patterns in asthma using multi-omics characterization"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilin","family":"Ying","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Liao","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jing","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Zhou","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yue","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boda","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]},{"name":"Biotechnology Innovation Drug Application and Transformation Key Laboratory of Sichuan Province, North Sichuan Medical College","place":["Nanchong, China"]},{"name":"Institute of Nanomedicine Innovation and Translational Research, Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]},{"name":"Institute of Integrated Traditional Chinese and Western Medicine, North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3967\/bes2025.042","article-title":"The disease burden of asthma in China, 1990 to 2021 and projections to 2050: Based on the Global Burden of Disease 2021","volume":"38","author":"Zhang","year":"2025","journal-title":"BioMed Environ Sci"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11172764","article-title":"Current understanding of asthma pathogenesis and biomarkers","volume":"11","author":"Habib","year":"2022","journal-title":"Cells"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/all.15054","article-title":"Advances and highlights in asthma in 2021","volume":"76","author":"Agache","year":"2021","journal-title":"Allergy"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2301619","DOI":"10.1183\/13993003.01619-2023","article-title":"Airway remodelling in asthma and the epithelium: on the edge of a new era","volume":"63","author":"Varricchi","year":"2024","journal-title":"Eur Respir J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2021.100969","article-title":"Corticosteroid resistance in asthma: Cellular and molecular mechanisms","volume":"85","author":"Caramori","year":"2022","journal-title":"Mol Aspects Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.cytogfr.2023.03.002","article-title":"Pathogenic mechanisms of glucocorticoid-induced osteoporosis","volume":"70","author":"Chen","year":"2023","journal-title":"Cytokine Growth Factor Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg8335","article-title":"Glucocorticoid-induced loss of beneficial gut bacterial extracellular vesicles is associated with the pathogenesis of osteonecrosis","volume":"8","author":"Chen","year":"2022","journal-title":"Sci Adv"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2021-0081","article-title":"Concepts of advanced therapeutic delivery systems for the management of remodeling and inflammation in airway diseases","volume":"14","author":"Dhanjal","year":"2022","journal-title":"Future Med Chem"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2024.116063","article-title":"Network pharmacology analysis and experimental validation of Xiao-Qing-Long-Tang's therapeutic effects against neutrophilic asthma","volume":"243","author":"Chen","year":"2024","journal-title":"J Pharm BioMed Anal"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1409128","article-title":"Traditional Chinese medicine to improve immune imbalance of asthma: focus on the adjustment of gut microbiota","volume":"15","author":"Lu","year":"2024","journal-title":"Front Microbiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156478","article-title":"Effectiveness and safety of Suhuang Zhike capsules in adults with asthma: A multicenter, randomized, double-blinded, placebo-controlled trial","volume":"141","author":"Pan","year":"2025","journal-title":"Phytomedicine"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.19852\/j.cnki.jtcm.20220408.003","article-title":"Integration strategy of network pharmacology in Traditional Chinese Medicine: a narrative review","volume":"42","author":"Jiashuo","year":"2022","journal-title":"J Tradit Chin Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1031051","article-title":"Multi-omics approaches for in-depth understanding of therapeutic mechanism for Traditional Chinese Medicine","volume":"13","author":"Zhu","year":"2022","journal-title":"Front Pharmacol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s13020-021-00521-3","article-title":"Exploring biological basis of Syndrome differentiation in coronary heart disease patients with two distinct Syndromes by integrated multi-omics and network pharmacology strategy","volume":"16","author":"Wu","year":"2021","journal-title":"Chin Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1022627","article-title":"Exploring the \"gene-protein-metabolite\" network of coronary heart disease with phlegm and blood stasis syndrome by integrated multi-omics strategy","volume":"13","author":"Yang","year":"2022","journal-title":"Front Pharmacol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/ar.25018","article-title":"Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV\/AIDS immunological nonresponders","volume":"306","author":"Ji","year":"2023","journal-title":"Anat Rec (Hoboken)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1208480","article-title":"Differentiation in TCM patterns of chronic obstructive pulmonary disease by comprehensive metabolomic and lipidomic characterization","volume":"14","author":"Li","year":"2023","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"72","DOI":"10.21037\/hbsn-2025-129","article-title":"Chinese expert consensus on conversion and perioperative therapy of primary liver cancer (2024 edition)","volume":"15","author":"Wang","year":"2026","journal-title":"Hepatobiliary Surg Nutr"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.13288\/j.11-2166\/r.2016.22.022","article-title":"Diagnostic criteria for Traditional Chinese Medicine syndromes of bronchial asthma (2016 version)","volume":"57","author":"Li","year":"2016","journal-title":"J Traditional Chin Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2678","article-title":"Asthma phenotypes: the evolution from clinical to molecular approaches","volume":"18","author":"Wenzel","year":"2012","journal-title":"Nat Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/587234","article-title":"Investigation into the influence of physician for treatment based on syndrome differentiation","volume":"2013","author":"Jiang","year":"2013","journal-title":"Evid Based Complement Alternat Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.980650","article-title":"Multi-omics approaches for deciphering the complexity of traditional Chinese medicine syndromes in stroke: A systematic review","volume":"13","author":"Liu","year":"2022","journal-title":"Front Pharmacol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.5c07657","article-title":"Multiomics and machine learning reveal distinct immune-metabolic signatures and diagnostic biomarkers for asthma inflammatory endotypes","volume":"10","author":"Liu","year":"2025","journal-title":"ACS Omega"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/falgy.2024.1496392","article-title":"Unraveling heterogeneity and treatment of asthma through integrating multi-omics data","volume":"5","author":"Zhang","year":"2024","journal-title":"Front Allergy"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11121299","article-title":"Microbiome research and multi-omics integration for personalized medicine in asthma","volume":"11","author":"Logotheti","year":"2021","journal-title":"J Pers Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2025.101132","article-title":"Multi-omics identifies severe asthma endotypes linked to Streptococcus dysbiosis and lipid metabolic dysregulation","volume":"18","author":"Liu","year":"2025","journal-title":"World Allergy Organ J"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/biom15020182","article-title":"Possible involvement of lysophospholipids in severe asthma as novel lipid mediators","volume":"15","author":"Kume","year":"2025","journal-title":"Biomolecules"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/all.14450","article-title":"Lysophosphatidylserine induces eosinophil extracellular trap formation and degranulation: Implications in severe asthma","volume":"75","author":"Kim","year":"2020","journal-title":"Allergy"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2014.6.1.61","article-title":"Bioactive lysophosphatidylcholine 16:0 and 18:0 are elevated in lungs of asthmatic subjects","volume":"6","author":"Yoder","year":"2014","journal-title":"Allergy Asthma Immunol Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1159\/000342430","article-title":"Francisella tularensis alters human neutrophil gene expression: insights into the molecular basis of delayed neutrophil apoptosis","volume":"5","author":"Schwartz","year":"2013","journal-title":"J Innate Immun"},{"key":"B31","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41392-020-00443-w","article-title":"Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2018.08.001","article-title":"Prostaglandins in asthma and allergic diseases","volume":"193","author":"Peebles","year":"2019","journal-title":"Pharmacol Ther"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22315","article-title":"Translating transcription: proteomics in chronic rhinosinusitis with nasal polyps reveals significant discordance with messenger RNA expression","volume":"9","author":"Workman","year":"2019","journal-title":"Int Forum Allergy Rhinol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13223-019-0382-x","article-title":"Whole blood vs PBMC: compartmental differences in gene expression profiling exemplified in asthma","volume":"15","author":"He","year":"2019","journal-title":"Allergy Asthma Clin Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.866116","article-title":"The role of RNA m6A methylation in lipid metabolism","volume":"13","author":"Wang","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179425","article-title":"Specific microRNA profile associated with inflammation and lipid metabolism for stratifying allergic asthma severity","volume":"25","author":"Escolar-Pe\u00f1a","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.adx8300","article-title":"The ubiquitin E3 ligase HRD1 restricts hepatic lipid metabolism by suppressing PPAR\u03b1-driven m6A RNA modification","volume":"19","author":"Kim","year":"2026","journal-title":"Sci Signal"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13061342","article-title":"Inflammation in asthma: mechanistic insights and the role of biologics in therapeutic frontiers","volume":"13","author":"Reza","year":"2025","journal-title":"Biomedicines"},{"key":"B39","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/s12864-023-09795-3","article-title":"Lipid metabolism-related genes are involved in the occurrence of asthma and regulate the immune microenvironment","volume":"25","author":"Jia","year":"2024","journal-title":"BMC Genomics"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156470","article-title":"Integrated transcriptomics and network pharmacology to reveal the mechanism of Physochlainae Radix in the treatment of asthma","volume":"139","author":"Tan","year":"2025","journal-title":"Phytomedicine"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2026.117368","article-title":"FOXA1-mediated CEPT1 deficiency in airway epithelium drives asthma via an ER stress-mitochondrial dysfunction axis","volume":"45","author":"Chen","year":"2026","journal-title":"Cell Rep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"100166","DOI":"10.1074\/jbc.RA120.015997","article-title":"ABCA13 dysfunction associated with psychiatric disorders causes impaired cholesterol trafficking","volume":"296","author":"Nakato","year":"2021","journal-title":"J Biol Chem"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.21037\/jtd-23-1628","article-title":"Mechanistic analysis of Th2-type inflammatory factors in asthma","volume":"15","author":"Qin","year":"2023","journal-title":"J Thorac Dis"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.01.007","article-title":"The role of lung and gut microbiota in the pathology of asthma","volume":"52","author":"Barcik","year":"2020","journal-title":"Immunity"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2025.101057","article-title":"From gums to moods: Exploring the impact of the oral microbiota on depression","volume":"48","author":"Singh Solorzano","year":"2025","journal-title":"Brain Behav Immun Health"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/falgy.2023.1120999","article-title":"The role of the respiratory microbiome in asthma","volume":"4","author":"Campbell","year":"2023","journal-title":"Front Allergy"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1922660\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:25:14Z","timestamp":1789453514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1922660\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2026.1922660"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1922660","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"1922660"}}