Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

Authors

Capucine Durand, Laurye-Anne Eveillard, Mathilde Labouret, Florence Aeschlimann, Alexandre Belot, Karine Brochard, Benoit Chassaing, Priscilla Boizeau, Rym Boulkedid, Aurélia Carbasse, Bilade Cherqaoui, Cécile Dumaine, Anne Dumay, Cécile Frachette, Véronique Hentgen, Cécile Kedzia, Therese Kolta, Isabelle Koné-Paut, Quentin Lamy-Besnier, Sophie Guilmin-Crepon, Lara Lima-Antoine, Pascal Pillet, Pierre Quartier, Stéphanie Tellier, Julien Tourneur-Marsille, Heloise Reumaux, Caroline Vinit, Emilie Viennois, Ulrich Meinzer

Published in

Gut microbes. Volume 18. Issue 1. Pages 2728351. Dec 31, 2026. Epub Sep 10, 2026.

Abstract

Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host-microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p = 0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p = 0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host-microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.

PMID:
42720258
Bibliographic data and abstract were imported from PubMed on 10 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.