ArticleArthritis & rheumatology (Hoboken, N.J.)2021
The Pretreatment Gut Microbiome Is Associated With Lack of Response to Methotrexate in New-Onset Rheumatoid Arthritis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Artificial intelligence in rheumatoid arthritis: current applications and future perspectives.Frontiers in medicine · 2026Pooled it
- Baseline gut microbiome and metabolites are correlated with changes in alcohol consumption in participants in a randomized Zonisamide clinical trial.Scientific reports · 2025Trial
- Sustained Drug Treatment Alters the Gut Microbiota in Rheumatoid Arthritis.Frontiers in immunology · 2021Trial
- Exploring the gut microbiome and metabolomic interactions of antimetabolite drugs to optimize therapy.Gut microbes · 2026Review
- Gut microbiota in early and established stages of rheumatoid arthritis: from pathogenesis to promising prevention and treatment.Annals of medicine · 2026Review
- The Gut Microbiota in Rheumatoid Arthritis: Evaluation of Microbial Profiles, Disease Activity, Biomarkers, and Treatment Response.Mediterranean journal of rheumatology · 2026Review
- Article
- Gut Microbial Functional Ecology and Microbiota-Derived Metabolites in Rheumatoid Arthritis Autoimmunity.Cells · 2026Review
- Recent antibiotic exposure and response to treatment of juvenile idiopathic arthritis: a retrospective cohort study.Arthritis research & therapy · 2026Article
- Intestinal microbiota and arthritis.EULAR rheumatology open · 2026Review
- The microbial metabolome: remodeling the therapeutic landscape in hematologic malignancies.NPJ biofilms and microbiomes · 2026Review
- Multi-cohort Analysis Reveals Microbiome Signatures Associated with Drug Response in New-Onset Rheumatoid Arthritis.bioRxiv : the preprint server for biology · 2026Article
- Microbial metabolism of methotrexate produces a STAT3 signaling molecule that alleviates gut inflammation.bioRxiv : the preprint server for biology · 2026Article
- The Oral-Gut-Immune-Nutrition Axis in Rheumatoid Arthritis: Molecular Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Pharmacomicrobiomics in Psoriasis: Microbiome-Drug Interactions Across Systemic Treatments.Life (Basel, Switzerland) · 2026Review
- Pathogenic Drivers of Difficult-to-Treat Rheumatoid Arthritis: Synovium and Beyond.International journal of molecular sciences · 2026Review
- Fasting and Nutrition as Promising Treatment Strategies for Women with Rheumatoid Arthritis in Transitional Hormonal Stages.Nutrients · 2026Review
- Multiomics Analyses Reveal an Essential Role of Tryptophan in Treatment of csDMARDs in Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Clinical Significance of Gut Microbiota Community Types for Long-Term Response to Fecal Microbiota Transplantation in Patients With Psoriatic Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Short-chain fatty acids and their gut microbial pathways distinguish rheumatoid arthritis in discordant monozygotic twins.Annals of the rheumatic diseases · 2026Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
Abstract
objectiveAlthough oral methotrexate (MTX) remains the anchor drug for rheumatoid arthritis (RA), up to 50% of patients do not achieve a clinically adequate outcome. In addition, there is a lack of prognostic tools for treatment response prior to drug initiation. This study was undertaken to investigate whether interindividual differences in the human gut microbiome can aid in the prediction of MTX efficacy in new-onset RA.
methodsWe performed 16S ribosomal RNA gene and shotgun metagenomic sequencing on the baseline gut microbiomes of drug-naive patients with new-onset RA (n = 26). Results were validated in an additional independent cohort (n = 21). To gain insight into potential microbial mechanisms, we conducted ex vivo experiments coupled with metabolomics analysis to evaluate the association between microbiome-driven MTX depletion and clinical response.
resultsOur analysis revealed significant associations of the abundance of gut bacterial taxa and their genes with future clinical response (q < 0.05), including orthologs related to purine and MTX metabolism. Machine learning techniques were applied to the metagenomic data, resulting in a microbiome-based model that predicted lack of response to MTX in an independent group of patients. Finally, MTX levels remaining after ex vivo incubation with distal gut samples from pretreatment RA patients significantly correlated with the magnitude of future clinical response, suggesting a possible direct effect of the gut microbiome on MTX metabolism and treatment outcomes.
conclusionTaken together, these findings are the first step toward predicting lack of response to oral MTX in patients with new-onset RA and support the value of the gut microbiome as a possible prognostic tool and as a potential target in RA therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.