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The Pretreatment Gut Microbiome Is Associated With LackĀ of Response to Methotrexate in New-Onset Rheumatoid Arthritis.
- Source :
-
Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2021 Jun; Vol. 73 (6), pp. 931-942. Date of Electronic Publication: 2021 May 02. - Publication Year :
- 2021
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Abstract
- Objective: Although 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.<br />Methods: We 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.<br />Results: Our 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.<br />Conclusion: Taken 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.<br /> (© 2020, American College of Rheumatology.)
- Subjects :
- Administration, Oral
Adult
Antirheumatic Agents metabolism
Arthritis, Rheumatoid microbiology
Arthritis, Rheumatoid physiopathology
Bacteroidetes genetics
Bacteroidetes metabolism
Clostridiales genetics
Clostridiales metabolism
Cohort Studies
Escherichia genetics
Escherichia metabolism
Euryarchaeota genetics
Euryarchaeota metabolism
Female
Firmicutes genetics
Firmicutes metabolism
Humans
Machine Learning
Male
Metabolomics
Metagenomics
Methotrexate metabolism
Middle Aged
Prognosis
RNA, Ribosomal, 16S
Shigella genetics
Shigella metabolism
Treatment Outcome
Antirheumatic Agents therapeutic use
Arthritis, Rheumatoid drug therapy
Gastrointestinal Microbiome genetics
Methotrexate therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2326-5205
- Volume :
- 73
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Arthritis & rheumatology (Hoboken, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 33314800
- Full Text :
- https://doi.org/10.1002/art.41622