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Sci Transl Med. 2017 Feb 8;9(376). pii: eaaf9655. doi: 10.1126/scitranslmed.aaf9655.

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

Author information

1
Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD), Weill Cornell Medicine, New York, NY 10021, USA.
2
College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
3
Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
4
Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94709, USA.
5
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
6
Division of Biostatistics and Epidemiology, Weill Cornell Medical College, New York, NY 10065, USA.
7
Hospital for Special Surgery, New York, NY 10021, USA.
8
Jill Roberts Center for IBD, Weill Cornell Medicine, New York, NY 10021, USA.
9
Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
10
Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD), Weill Cornell Medicine, New York, NY 10021, USA. ral2006@med.cornell.edu.

Abstract

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.

PMID:
28179509
DOI:
10.1126/scitranslmed.aaf9655
[Indexed for MEDLINE]

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