TY - JOUR
T1 - Interleukin-17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin-25–Driven Intestinal Inflammation
AU - Manasson, Julia
AU - Wallach, David S.
AU - Guggino, Giuliana
AU - Stapylton, Matthew
AU - Badri, Michelle H.
AU - Solomon, Gary
AU - Reddy, Soumya M.
AU - Coras, Roxana
AU - Aksenov, Alexander A.
AU - Jones, Drew R.
AU - Girija, Parvathy V.
AU - Neimann, Andrea L.
AU - Heguy, Adriana
AU - Segal, Leopoldo N.
AU - Dorrestein, Pieter C.
AU - Bonneau, Richard
AU - Guma, Monica
AU - Ciccia, Francesco
AU - Ubeda, Carles
AU - Clemente, Jose C.
AU - Scher, Jose U.
N1 - Publisher Copyright:
© 2019, American College of Rheumatology
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - Antibodies, Monoclonal, Humanized/pharmacology
KW - Arthritis, Psoriatic/drug therapy
KW - Female
KW - Gastrointestinal Microbiome/drug effects
KW - Humans
KW - Inflammation/metabolism
KW - Interleukin-17/immunology
KW - Intestinal Mucosa/metabolism
KW - Intestines/drug effects
KW - Male
KW - Middle Aged
KW - Spondylarthritis/drug therapy
KW - Tumor Necrosis Factor Inhibitors/pharmacology
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U2 - 10.1002/art.41169
DO - 10.1002/art.41169
M3 - Article
C2 - 31729183
AN - SCOPUS:85081304661
SN - 2326-5191
VL - 72
SP - 645
EP - 657
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 4
ER -