Gut Microbiome Signatures Forecast Clinical Response to Methotrexate in Treatment-Naive Early Rheumatoid Arthritis Patients
Oral methotrexate (MTX) is the first-line treatment for newly diagnosed rheumatoid arthritis (RA) patients. However, up to 50% of patients do not respond adequately to MTX and need other therapeutic interventions. Failure to respond to MTX during the first three months, which is known as the critical window of opportunity for effective RA treatment, can significantly impact disease progression. Therefore, accurately predicting MTX response is crucial for managing RA disease progression. Recent studies have revealed an association between the gut microbiome and the response to MTX in treatment-naive RA patients. However, most of these studies primarily used 16S rRNA gene amplicon sequencing data, which primarily provides taxonomic resolution at the genus level. One study utilized whole-genome shotgun (WGS) sequencing data, but it did not employ WGS-based taxonomic profiles to identify its association with the MTX response. Additionally, this study applied an arbitrary criterion to determine MTX response instead of using the standardized EULAR response criteria, which limits the clinical translation of its findings. Our study aims to address these limitations and more thoroughly investigate whether the gut microbiome can reliably predict MTX response in treatment-naive RA patients.