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

Autor:	Lima SF; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Pires S; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Rupert A; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA; Jill Roberts Center for IBD, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Oguntunmibi S; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Jin WB; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA., Marderstein A; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA., Funez-dePagnier G; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA; Jill Roberts Center for IBD, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Maldarelli G; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Viladomiu M; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Putzel G; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA., Yang W; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Tran N; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA; Jill Roberts Center for IBD, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Xiang G; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA; Jill Roberts Center for IBD, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Grier A; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA., Guo CJ; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA., Lukin D; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA; Jill Roberts Center for IBD, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Mandl LA; Division of Rheumatology, Hospital for Special Surgery and Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Scherl EJ; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA; Jill Roberts Center for IBD, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA., Longman RS; Jill Roberts Institute for Research in IBD, Weill Cornell Medicine, New York, NY 10065, USA; Division of Gastroenterology and Hepatology, Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA; Jill Roberts Center for IBD, NewYork-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA. Electronic address: ral2006@med.cornell.edu.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Mar 19; Vol. 5 (3), pp. 101431. Date of Electronic Publication: 2024 Feb 19.
DOI:	10.1016/j.xcrm.2024.101431
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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