The Gut Microbiome Regulates the Clinical Efficacy of Sulfasalazine Therapy for IBD-associated Spondyloarthritis

Overview

Journal Cell Rep Med

Publisher Cell Press

Specialties Biology
General Medicine

Date 2024 Feb 20

PMID 38378002

Authors

Svetlana F Lima

Silvia Pires

Amanda Rupert

Seun Oguntunmibi

Wen-Bing Jin

Andrew Marderstein

Gabriela Funez-dePagnier

Grace Maldarelli

Monica Viladomiu

Gregory Putzel

Wei Yang

Nancy Tran

Grace Xiang

Alex Grier

Chun-Jun Guo

Dana Lukin

Lisa A Mandl

Ellen J Scherl

Randy S Longman

Affiliations

Soon will be listed here.

Abstract

Sulfasalazine is a prodrug known to be effective for the treatment of inflammatory bowel disease (IBD)-associated peripheral spondyloarthritis (pSpA), but the mechanistic role for the gut microbiome in regulating its clinical efficacy is not well understood. Here, treatment of 22 IBD-pSpA subjects with sulfasalazine identifies clinical responders with a gut microbiome enriched in Faecalibacterium prausnitzii and the capacity for butyrate production. Sulfapyridine promotes butyrate production and transcription of the butyrate synthesis gene but in F. prausnitzii in vitro, which is suppressed by excess folate. Sulfasalazine therapy enhances fecal butyrate production and limits colitis in wild-type and gnotobiotic mice colonized with responder, but not non-responder, microbiomes. F. prausnitzii is sufficient to restore sulfasalazine protection from colitis in gnotobiotic mice colonized with non-responder microbiomes. These findings reveal a mechanistic link between the efficacy of sulfasalazine therapy and the gut microbiome with the potential to guide diagnostic and therapeutic approaches for IBD-pSpA.

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