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Interleukin‐17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin‐25–Driven Intestinal Inflammation
Author(s) -
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.
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41169
Subject(s) - immunology , microbiome , dysbiosis , subclinical infection , biology , tumor necrosis factor alpha , interleukin , interleukin 22 , gut flora , microbiology and biotechnology , medicine , cytokine , bioinformatics
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.