IgA-coatedE. colienriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation.
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 16Sribosomal RNA-based analysis (IgA-seq) revealed a selective enrichment in IgA-coatedEscherichia coliin patients with Crohn's disease-associated SpA (CD-SpA) compared to CD alone.E. coliisolates from CD-SpA-derived IgA-coated bacteria were similar in genotype and phenotype to an adherent-invasiveE. coli(AIEC) pathotype. In comparison to non-AIECE. coli, colonization of germ-free mice with CD-SpAE. coliisolates 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-derivedE. colilead 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.
Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD), Weill Cornell Medicine, New York, NY 10021, USA.
Monica
M
Viladomiu
Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD), Weill Cornell Medicine, New York, NY 10021, USA.
Charles
C
Kivolowitz
Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD), Weill Cornell Medicine, New York, NY 10021, USA.
Ahmed
A
Abdulhamid
College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Belgin
B
Dogan
Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD), Weill Cornell Medicine, New York, NY 10021, USA.
Daniel
D
Victorio
Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD), Weill Cornell Medicine, New York, NY 10021, USA.
Jim G
JG
Castellanos
Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD), Weill Cornell Medicine, New York, NY 10021, USA.
Viola
V
Woo
Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
Fei
F
Teng
Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
Nhan L
NL
Tran
Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94709, USA.
Andrew
A
Sczesnak
Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD), Weill Cornell Medicine, New York, NY 10021, USA.
Christina
C
Chai
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Myunghoo
M
Kim
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Gretchen E
GE
Diehl
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Nadim J
NJ
Ajami
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Joseph F
JF
Petrosino
Division of Biostatistics and Epidemiology, Weill Cornell Medical College, New York, NY 10065, USA.
Xi K
XK
Zhou
Hospital for Special Surgery, New York, NY 10021, USA.
Sergio
S
Schwartzman
Hospital for Special Surgery, New York, NY 10021, USA.
Lisa A
LA
Mandl
Jill Roberts Center for IBD, Weill Cornell Medicine, New York, NY 10021, USA.
Meira
M
Abramowitz
Jill Roberts Center for IBD, Weill Cornell Medicine, New York, NY 10021, USA.
Vinita
V
Jacob
Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Brian
B
Bosworth
Jill Roberts Center for IBD, Weill Cornell Medicine, New York, NY 10021, USA.
Adam
A
Steinlauf
Jill Roberts Center for IBD, Weill Cornell Medicine, New York, NY 10021, USA.
Ellen J
EJ
Scherl
Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
Hsin-Jung Joyce
HJ
Wu
College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Kenneth W
KW
Simpson
Jill Roberts Institute for Research in Inflammatory Bowel Disease (IBD), Weill Cornell Medicine, New York, NY 10021, USA. ral2006@med.cornell.edu.|Jill Roberts Center for IBD, Weill Cornell Medicine, New York, NY 10021, USA.
Randy S
RS
Longman
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000382:microbiology; D003424:Crohn Disease / Q000150:complications / Q000276:immunology* / Q000382:microbiology*; D016264:Dextran Sulfate; D004848:Epithelium / Q000276:immunology; D004926:Escherichia coli / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000378:metabolism*; D016130:Immunophenotyping; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D016753:Interleukin-10 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D007596:Joints / Q000473:pathology; D008810:Mice, Inbred C57BL; D025241:Spondylarthritis / Q000150:complications / Q000276:immunology* / Q000382:microbiology*; D058504:Th17 Cells / Q000276:immunology*
D015415:Biomarkers; D007070:Immunoglobulin A; D053759:Interleukin-23; D016753:Interleukin-10; D016264:Dextran Sulfate