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

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RESEARCH PRODUCT

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

Soumya M. Reddy Matthew Stapylton Drew R. Jones Richard Bonneau Alexander A. Aksenov Carles Ubeda Pieter C. Dorrestein Monica Guma Michelle H. Badri Andrea L. Neimann Jose C. Clemente Gary Solomon Giuliana Guggino Jose U. Scher Francesco Ciccia Adriana Heguy Leopoldo N. Segal Roxana Coras Julia Manasson Parvathy V. Girija David S. Wallach

subject

Male 0301 basic medicine Arthritis Psoriatic 0302 clinical medicine Interleukin 25 Monoclonal 2.1 Biological and endogenous factors Immunology and Allergy Medicine Aetiology Intestinal Mucosa Candida albicans Humanized Subclinical infection biology Interleukin-17 Innate lymphoid cell Middle Aged Intestines Public Health and Health Services Female Tumor necrosis factor alpha Interleukin 17 Clinical Sciences Immunology Antibodies Monoclonal Humanized Autoimmune Disease Antibodies Article 03 medical and health sciences Rheumatology Clinical Research Spondylarthritis Humans Microbiome Inflammation 030203 arthritis & rheumatology business.industry Arthritis Inflammatory and immune system Arthritis Psoriatic biology.organism_classification medicine.disease Arthritis & Rheumatology Gastrointestinal Microbiome 030104 developmental biology Immunology Tumor Necrosis Factor Inhibitors Digestive Diseases business

description

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.

year	journal	country	edition	language
2020-01-01

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