Interleukin‐17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin‐25–Driven Intestinal Inflammation. Issue 4 (12th March 2020)

• Record Type: Journal Article
• Authors: Manasson, Julia; Wallach, David S.; Guggino, Giuliana; Stapylton, Matthew; Badri, Michelle H.; Solomon, Gary; Reddy, Soumya M.; Coras, Roxana; Aksenov, Alexander A.; Jones, Drew R.; Girija, Parvathy V.; Neimann, Andrea L.; Heguy, Adriana; Segal, Leopoldo N.; Dorrestein, Pieter C.; Bonneau, Richard; Guma, Monica; Ciccia, Francesco; Ubeda, Carles; Clemente, Jose C.; Scher, Jose U.
• Is Part Of: Arthritis & rheumatology. Volume 72:Issue 4(2020)
• Page Start: 645
• Page End: 657
• Publication Date: 2020-03-12
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.41169
• Languages: English
• ISSNs: 2326-5191

Abstract

Abstract : Objective: To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome in psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients. Methods: Fecal samples from PsA/SpA patients pre‐ and posttreatment with tumor necrosis factor inhibitors (TNFi; n = 15) or an anti–interleukin‐17A monoclonal antibody inhibitor (IL‐17i; n = 14) underwent sequencing (16S ribosomal RNA, internal transcribed spacer and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL‐17i (n = 5) were analyzed for expression of IL‐23/Th17–related cytokines, IL‐25/IL‐17E–producing cells, and type 2 innate lymphoid cells (ILC2s). Results: There were significant shifts in abundance of specific taxa after treatment with IL‐17i compared to TNFi, particularly Clostridiales ( P = 0.016) and Candida albicans ( P = 0.041). These subclinical alterations correlated with changes in bacterial community co‐occurrence, metabolic pathways, IL‐23/Th17–related cytokines, and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL‐25/IL‐17E–producing tuft cells and ILC2s ( P < 0.05), compared to pre–IL‐17i treatment levels. Conclusion: In a subgroup of SpA patients, the initiation of IL‐17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C albicans . Further, IL‐17i–related CD was associated with overexpression of IL‐25/IL‐17E–producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL‐17 pathway and the (sub)clinical gut inflammation observed in SpA.