Clinical multi-omics reveals the role of Tuomin Zhiti Decoction Intervention in Allergic Rhinitis from the perspective of biological network

Background Increasing evidence showed that seasonal allergic rhinitis (SAR), as an allergy disease, could be alleviated with traditional Chinese medicine (TCM) formula, one example being Tuomin Zhiti Decoction (TZD). However, as a complex composition of TCM herbs, the mechanism of TZD in the treatment of SAR remain unclear. Purpose Uncover the mechanism of TZD for treating SAR based on computational analysis and clinical multi-omics experiments. Study design Integrate computational analysis including network target analysis and machine learning algorithms with clinical multi-omics experiments and public omics data. Methods By analyzing TZD’s composition through a network-based method, we identified the biological effects of each compound, constructing a comprehensive biological network to elucidate TZD’s molecular and pathway mechanisms against AR. Single-arm clinical trials on the gut microbiome and serum transcriptomics corroborated our computational insights. Further validation through public omics data highlighted key TZD compounds, paving the way for future research. Results TZD was discovered to exert a regulatory effect on various modules associated with AR, as demonstrated by the constructed biological network. Insights from gut microbiome and serum transcriptomics in clinical trials, where immune-related microbiomes represented by Prevotella, as well as pathways and biological processes including antigen processing and presentation, activation and regulating immune cell surface receptor, were markedly enriched ( P value < 0.05), indicated that TZD played a pivotal role in modulating immune processes and the immune cells against AR. With the verification of multi-omics, it was determined that TZD potentially influences immune responses and downstream immune cells like CD4+ T cells, through both direct mechanisms involving antigen and indirect mechanisms mediated by gut microbiomes in the treatment of AR. Conclusion Through combination of computational prediction and analysis together with clinical multi-omics, a network target based framework provided a new insight for uncovering the mechanism of TZD for treating AR. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ChiCTR2100044839 ### Funding Statement the Fundamental Research Funds for the Central Universities(No.2023-JYB-JBZD-009) and High level Key Discipline of National Administration of Traditional Chinese Medicine - Traditional Chinese constitutional medicine(No.zyyzdxk-2023251). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Ethics Committee of Shanghai East Hospital gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. All data produced in the present work are contained in the manuscript. * TESS : Total Eye Symptom Score; TNSS : Total Nasal Symptom Score; TZD : Tuomin-Zhiti-Decoction; AR : Allergic Rhinitis; SAR : Seasonal Allergic Rhinitis; RQLQ : Rhino conjunctivitis Quality of Life Questionnaire; TCM : Traditional Chinese Medicine.