Interleukin-17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin-25-Driven Intestinal Inflammation.

Arthritis & rheumatology (Hoboken, N.J.) 2020 Apr

filter terms:

To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome in psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients. 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). 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. 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. © 2019, American College of Rheumatology.

Citation

Julia Manasson, David S Wallach, Giuliana Guggino, Matthew Stapylton, Michelle H Badri, Gary Solomon, Soumya M Reddy, Roxana Coras, Alexander A Aksenov, Drew R Jones, Parvathy V Girija, Andrea L Neimann, Adriana Heguy, Leopoldo N Segal, Pieter C Dorrestein, Richard Bonneau, Monica Guma, Francesco Ciccia, Carles Ubeda, Jose C Clemente, Jose U Scher. Interleukin-17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin-25-Driven Intestinal Inflammation. Arthritis & rheumatology (Hoboken, N.J.). 2020 Apr;72(4):645-657