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Multi-cohort Analysis Reveals Microbiome Signatures Associated with Drug Response in New-Onset Rheumatoid Arthritis.

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Gut microbiome signatures predict methotrexate response in rheumatoid arthritis patients. Consistent microbial patterns across patient cohorts suggest potential for microbiome-based precision medicine in early RA treatment.

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Area of Science:

  • Microbiome research
  • Rheumatology
  • Pharmacogenomics

Background:

  • The human gut microbiome significantly impacts treatment efficacy.
  • Generalizability of microbiome drug response signatures across patient cohorts is largely unknown.
  • Understanding these signatures is crucial for personalized medicine in rheumatoid arthritis (RA).

Purpose of the Study:

  • To investigate cross-cohort microbial signatures associated with methotrexate (MTX) response in new-onset RA patients.
  • To determine if gut microbiome profiles can predict future MTX treatment outcomes.
  • To explore the role of specific microbial taxa and functions in MTX response.

Main Methods:

  • Multi-cohort analysis of 100 new-onset RA patients across 3 cohorts.
  • Analysis of pre-treatment gut microbiome community structure and function.
  • Comparison of microbiome profiles between MTX responders and non-responders (MTX-NR).
  • Assessment of microbial functions, including nucleotide metabolism and histidine metabolism.
  • Identification of candidate MTX-degrading genes.

Main Results:

  • Pre-treatment gut microbiome differed significantly between MTX responders and MTX-NR.
  • MTX-NR showed depletion of *Bacteroides caccae* and enrichment of *Ruminococcus bromii*.
  • Key microbial functions, including folate metabolism, were depleted in MTX-NR.
  • Candidate MTX-degrading genes were enriched in MTX-NR.
  • Microbiome functional profiles demonstrated superior predictive power for MTX response compared to clinical metrics.

Conclusions:

  • Consistent gut microbiome signatures are associated with MTX response across different RA cohorts.
  • Microbiome analysis can predict MTX treatment outcomes in early RA.
  • These findings support the development of microbiome-based precision medicine strategies for RA patients.