The gut microbiome regulates the clinical efficacy of sulfasalazine therapy for IBD-associated spondyloarthritis

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number101431
JournalCell Reports Medicine
Volume5
Issue number3
DOIs
StatePublished - 19 Mar 2024
Externally publishedYes

Keywords

  • Faecalibacterium prausnitzii
  • butyrate
  • folate
  • inflammatory bowel disease
  • microbiome
  • spondyloarthritis
  • sulfasalazine

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