July 7, 2019  |  

IgA-coated E. coli enriched in Crohn’s disease spondyloarthritis promote TH17-dependent inflammation.

Authors: Viladomiu, Monica and Kivolowitz, Charles and Abdulhamid, Ahmed and Dogan, Belgin and Victorio, Daniel and Castellanos, Jim G and Woo, Viola and Teng, Fei and Tran, Nhan L and Sczesnak, Andrew and Chai, Christina and Kim, Myunghoo and Diehl, Gretchen E and Ajami, Nadim J and Petrosino, Joseph F and Zhou, Xi K and Schwartzman, Sergio and Mandl, Lisa A and Abramowitz, Meira and Jacob, Vinita and Bosworth, Brian and Steinlauf, Adam and Scherl, Ellen J and Wu, Hsin-Jung Joyce and Simpson, Kenneth W and Longman, Randy S

Peripheral spondyloarthritis (SpA) is a common extraintestinal manifestation in patients with active inflammatory bowel disease (IBD) characterized by inflammatory enthesitis, dactylitis, or synovitis of nonaxial joints. However, a mechanistic understanding of the link between intestinal inflammation and SpA has yet to emerge. We evaluated and functionally characterized the fecal microbiome of IBD patients with or without peripheral SpA. Coupling the sorting of immunoglobulin A (IgA)-coated microbiota with 16S ribosomal RNA-based analysis (IgA-seq) revealed a selective enrichment in IgA-coated Escherichia coli in patients with Crohn's disease-associated SpA (CD-SpA) compared to CD alone. E. coli isolates from CD-SpA-derived IgA-coated bacteria were similar in genotype and phenotype to an adherent-invasive E. coli (AIEC) pathotype. In comparison to non-AIEC E. coli, colonization of germ-free mice with CD-SpA E. coli isolates induced T helper 17 cell (TH17) mucosal immunity, which required the virulence-associated metabolic enzyme propanediol dehydratase (pduC). Modeling the increase in mucosal and systemic TH17 immunity we observed in CD-SpA patients, colonization of interleukin-10-deficient or K/BxN mice with CD-SpA-derived E. coli lead to more severe colitis or inflammatory arthritis, respectively. Collectively, these data reveal the power of IgA-seq to identify immunoreactive resident pathosymbionts that link mucosal and systemic TH17-dependent inflammation and offer microbial and immunophenotype stratification of CD-SpA that may guide medical and biologic therapy. Copyright © 2017, American Association for the Advancement of Science.

Journal: Science translational medicine
DOI: 10.1126/scitranslmed.aaf9655
Year: 2017

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