Gut Microbiome Modulation by Fiber Enhances RA Methotrexate Response, With Claire Daien, MD, PhD

Fiber supplementation significantly increased EULAR response rates and improved Th17/Treg balance in people with rheumatoid arthritis (RA) receiving methotrexate treatment, further supporting the gut–immune axis as a meaningful therapeutic target in the disease.

These findings are from the randomized, double-blind, placebo controlled SUPERFIBRE trial which was presented at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois, by Claire Daien, MD, PhD, Professor of Rheumatology at Université de Montpellier.

SUPERFIBRE was conducted in the wake of growing evidence that short-chain fatty acids produced by fiber-fermenting bacteria, especially Bacteroides fragilis, appear to promote immune tolerance by boosting Tregs and reducing proinflammatory Th17 cells. The trial enrolled 49 patients with active RA despite stable doses of csDMARDs randomized 1:1 to receive daily inulin (12 g/day) or placebo for 30 days.

In the trial, the mean DAS28 score was 3.86 (standard deviation, 0.61) at baseline, with most patients on MTX. By Day 30, 53.85% of patients in the fiber group achieved an EULAR response versus 21.74% in the placebo group (P = .04), with an odds ratio of 4.65 (95% CI, 1.15–18.9; P = .03) of achieving EULAR response compared to placebo, adjusted on compliance, baseline DAS28, age, BMI and sex.

Subgroup analyses revealed a strong interaction between fiber and MTX: among MTX-treated patients, the mean ΔDAS28 was −1.00 with fiber compared with 0.34 with placebo (P = .011). Low disease activity and remission on DAS28 were not significantly different between groups. The intervention was well-tolerated and compliance was over 90%.

HCPLive spoke with Daien to learn more about the new data supporting fiber supplementation to improve MTX response. She shared her excitement for the findings, which could enable a simple, low-cost enhancement for RA outcomes. She also discussed further research to be done with fiber, the gut microbiome, and RA.

"We had 4 times more EULAR responders in the fiber group than in the placebo group. So these are pretty exciting results that we don't know exactly how to explain today. Is it because of the anti inflammatory effects of the fiber through the... fatty acids increase? So this will be known when we'll have the results of our measures, but we don't know yet," Daien said.

Daien reported no disclosures.

Reference

Daien CI, Hellier JP, Salis Z, et al. Dietary Fiber Supplementation Enhances Methotrexate Response and Restores Th17/Treg Balance in Rheumatoid Arthritis: Results from the Superfibre Randomized Trial. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #LB15