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journal article·2026-02Open access

Multiomics Analyses Reveal an Essential Role of Tryptophan in Treatment of csDMARDs in Rheumatoid Arthritis

Congcong Jian, Jing Zhu, Jianhong Wu, Yan Zhang, Jianghua Chen, Huan Wang, Hengyan Liu, Ke Xu, Jiaxin Huang, Xiaoting Zhu, Yuanli Wei, Shilin Li, Tingting Wang, Xuan Huang, Qinghua Zou, Jie Zhang, Jiang Su, Xinming Du, Yaping Lu, Tianci Zhou, Yingtong Zhou, Minglong Tang, Bin Li, Xue Zhou, Qihao Wei, Qiulong Yan, Fanxin Zeng

Advanced Science· Volume 13· Issue 9
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Source abstract

Abstract

Abstract Rheumatoid arthritis (RA) is a autoimmune disease characterized by heterogeneity in response to conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs). This study aims to elucidate molecular differences in response mechanisms of RA patients to csDMARDs through multiomics approach, with particular focus on the role of tryptophan (Trp) in treatment. Plasma, fecal, and peripheral blood mononuclear cells (PBMCs) were collected for metabolomics, microbiomics, transcriptomics, single‐cell transcriptomics, proteomics, and phosphoproteomics analyses. Additionally, in vitro/vivo experiments and controlled clinical trial were conducted to validate the findings. Comprehensive analysis revealed significant alterations in Trp‐related metabolic profiles, microbiota composition, and immune cells, indicating the role of Trp in modulating therapeutic response to csDMARDs. In vitro experiments demonstrated that Trp significantly inhibited the proliferation of MH7A and PBMCs while reducing the secretion of IL‐1β, IL‐6, and TNF‐α. Furthermore, in vivo studies showed that Trp treatment decreased arthritis scores and histological scores in mice. Clinical data further confirmed that dietary supplementation with Trp significantly improved disease activity scores and alleviated inflammatory in RA patients. This study highlights the crucial regulatory role of Trp in RA therapy, providing novel insights for optimizing clinical treatment strategies for RA.
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Research context

OpenAlex topics: Rheumatoid Arthritis Research and Therapies · Autoimmune and Inflammatory Disorders Research · Immune Cell Function and Interaction

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Clinical Research Center Sichuan Clinical Research Center for Medical Imaging Dazhou Central Hospital Dazhou 635000 China

Medical School Sichuan University of Arts and Sciences Dazhou 635002 China

School of Basic Medical Science Chengdu University of Traditional Chinese Medicine Chengdu 611137 China

Department of Rheumatology and Immunology Sichuan Provincial People's Hospital Chengdu 610072 China

Department of Rheumatology and Immunology Dazhou Central Hospital Dazhou 635000 China

Department of Medical Oncology Cancer Center West China Hospital Sichuan University Chengdu 610041 China

Dazhou Vocational College of Chinese Medicine Dazhou 635000 China

North Sichuan Medical College Nanchong 637100 China

Mudanjiang Medical University Mudanjiang 157011 China

Medicine School of Henan University Kaifeng 450046 China

Institute of Basic Medicine and Forensic Medicine North Sichuan Medical College Nanchong 637100 China

Medical Research Center Beijing Chaoyang Hospital Capital Medical University Beijing 100000 China

Department of Rheumatology and Immunology First Affiliated Hospital of Army Medical University Chongqing 400038 China

Hubei Key Laboratory of Agricultural Bioinformatics College of Informatics Huazhong Agricultural University Wuhan 430070 China

Sinopharm (Wuhan) Medical Laboratory Co., Ltd. Wuhan 430000 China

Sinopharm (Wuhan) Precision Medical Technology Co., Ltd. Wuhan 430000 China

Department of Oncology The Affiliated Hospital of Southwest Medical University Luzhou 646000 China

The Fifth Affiliated Hospital of Southern Medical University Guangzhou 510900 China

Funding

Chengdu University of Traditional Chinese Medicine · Sichuan Provincial Administration of Traditional Chinese Medicine

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