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

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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Publication Details

Journal
Advanced Science
Published
2025-09-23
DOI
https://doi.org/10.1002/advs.202413170
Citations
1
Primary Topic
Rheumatoid Arthritis Research and Therapies
Type
article
Field-Weighted Citation Impact
1.67

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article

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

Hengyan Liu, Yingtong Zhou, Congcong Jian, Xueyan Du et al.
1 citations
Advanced Science
Rheumatoid Arthritis Research and Therapies
1.67
article

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

Hengyan Liu, Yingtong Zhou, Congcong Jian, Xueyan Du, Jiang Su, Qihao Wei, Qiulong Yan, Yuanli Wei, Qinghua Zou, Jing Zhu, Ya-Ping Lü, Xue Zhou, Xiaoting Zhu, Huan Wang, Bin Li, Jie Zhang, Jian Wu, Yan Zhang, Jianghua Chen, Shilin Li, Fanxin Zeng, Ke Xu, Tianyu Zhou, Xuan Huang, Jiaxin Huang, Minglong Tang, Tingting Wang
article en
1 citations

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.

Advanced ScienceVol. 13(9)
North Sichuan Medical University (CN), Army Medical University (CN), Henan University (CN), Huazhong Agricultural University (CN), Sichuan University (CN), West China Medical Center of Sichuan University (CN), Beijing Chao-Yang Hospital, Capital Medical University (CN), Sichuan University of Arts and Science (CN), Affiliated Hospital of Southwest Medical University (CN), Huzhou Vocational and Technical College (CN), Third Affiliated Hospital of Southern Medical University (CN), China National Pharmaceutical Group Corporation (China) (CN), Mudanjiang Medical University (CN), Fourth People's Hospital of Sichuan Province (CN), Sichuan Cancer Hospital (CN), The Affiliated Yongchuan Hospital of Chongqing Medical University (CN), Southwest Hospital (CN), Sichuan Provincial Hospital of Traditional Chinese Medicine (CN), Beijing Chaoyang Emergency Medical Center (CN), Dazhou Central Hospital (CN), Chengdu University of Traditional Chinese Medicine (CN), Southern Medical University (CN), Chongqing Medical University (CN)
Department of Science and Technology of Sichuan Province, Chengdu University of Traditional Chinese Medicine, Chengdu University, National Science and Technology Major Project
Openalex Percentile: Top 13%
Rheumatoid Arthritis Research and Therapies
1.67
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