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

Congcong Jian1,2,3, Jing Zhu4, Jianhong Wu5

  • 1Department of Clinical Research Center, Sichuan Clinical Research Center for Medical Imaging, Dazhou Central Hospital, Dazhou, 635000, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 23, 2025
PubMed

Insights

Rheumatoid arthritis (RA) patients show varied responses to treatments. This study reveals that tryptophan (Trp) significantly impacts treatment efficacy by modulating immune responses and inflammation in RA.

Area of Science:

  • Immunology
  • Metabolomics
  • Microbiomics

Background:

  • Rheumatoid arthritis (RA) exhibits heterogeneous responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).
  • Understanding molecular mechanisms underlying treatment response variability is crucial for optimizing RA therapy.

Purpose of the Study:

  • To investigate molecular differences in RA patient responses to csDMARDs using a multiomics approach.
  • To elucidate the specific role of tryptophan (Trp) in modulating therapeutic outcomes for RA patients.

Main Methods:

  • Multiomics analyses including metabolomics, microbiomics, transcriptomics, and proteomics on plasma, fecal, and PBMCs.
  • In vitro and in vivo experiments using cell lines and mouse models.
  • A controlled clinical trial to assess the effect of Trp supplementation in RA patients.

Main Results:

  • Significant alterations in Trp metabolism, gut microbiota, and immune cell profiles were observed in RA patients.
  • Tryptophan demonstrated inhibitory effects on immune cell proliferation and reduced pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α) in vitro.
  • In vivo and clinical studies confirmed that Trp supplementation improved arthritis scores, reduced inflammation, and enhanced disease activity in RA.

Conclusions:

  • Tryptophan plays a critical regulatory role in the therapeutic response to csDMARDs in rheumatoid arthritis.
  • Altered Trp metabolism and its modulation of immune pathways are key factors in RA treatment response.
  • Dietary Trp supplementation represents a promising strategy for improving clinical outcomes in RA patients.
Keywords:
csDMARDsmultiomics strategyrheumatoid arthritistreatment responsetryptophan

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