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

Monica Viladomiu, Charles Kivolowitz, Ahmed Abdulhamid, Belgin Dogan, Daniel Victorio, Jim G. Castellanos, Viola Woo, Fei Teng, Nhan L. Tran, Andrew Sczesnak, Christina Chai, Myunghoo Kim, Gretchen E. Diehl, Nadim J. Ajami, Joseph F. Petrosino, Xi K. Zhou, Sergio Schwartzman, Lisa A. Mandl, Meira Abramowitz, Vinita Jacob & 6 others Brian Bosworth, Adam Steinlauf, Ellen J. Scherl, Hsin-Jung Joyce Wu, Kenneth W. Simpson, Randy S. Longman

Research output: Contribution to journalArticle

57 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbereaaf9655
JournalScience Translational Medicine
Volume9
Issue number376
DOIs
StatePublished - Feb 8 2017

Fingerprint

Th17 Cells
Crohn Disease
Immunoglobulin A
Escherichia coli
Inflammation
Microbiota
Inflammatory Bowel Diseases
Propanediol Dehydratase
16S Ribosomal RNA
Mucosal Immunity
Biological Therapy
Synovitis
Colitis
Interleukin-10
Arthritis
Virulence
Immunity
Joints
Genotype
Bacteria

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Viladomiu, M., Kivolowitz, C., Abdulhamid, A., Dogan, B., Victorio, D., Castellanos, J. G., ... Longman, R. S. (2017). IgA-coated E. Coli enriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation. Science Translational Medicine, 9(376), [eaaf9655]. https://doi.org/10.1126/scitranslmed.aaf9655

IgA-coated E. Coli enriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation. / Viladomiu, Monica; Kivolowitz, Charles; Abdulhamid, Ahmed; Dogan, Belgin; Victorio, Daniel; Castellanos, Jim G.; Woo, Viola; Teng, Fei; Tran, Nhan L.; Sczesnak, Andrew; Chai, Christina; Kim, Myunghoo; Diehl, Gretchen E.; Ajami, Nadim J.; Petrosino, Joseph F.; Zhou, Xi K.; Schwartzman, Sergio; Mandl, Lisa A.; Abramowitz, Meira; Jacob, Vinita; Bosworth, Brian; Steinlauf, Adam; Scherl, Ellen J.; Wu, Hsin-Jung Joyce; Simpson, Kenneth W.; Longman, Randy S.

In: Science Translational Medicine, Vol. 9, No. 376, eaaf9655, 08.02.2017.

Research output: Contribution to journalArticle

Viladomiu, M, Kivolowitz, C, Abdulhamid, A, Dogan, B, Victorio, D, Castellanos, JG, Woo, V, Teng, F, Tran, NL, Sczesnak, A, Chai, C, Kim, M, Diehl, GE, Ajami, NJ, Petrosino, JF, Zhou, XK, Schwartzman, S, Mandl, LA, Abramowitz, M, Jacob, V, Bosworth, B, Steinlauf, A, Scherl, EJ, Wu, H-JJ, Simpson, KW & Longman, RS 2017, 'IgA-coated E. Coli enriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation', Science Translational Medicine, vol. 9, no. 376, eaaf9655. https://doi.org/10.1126/scitranslmed.aaf9655
Viladomiu M, Kivolowitz C, Abdulhamid A, Dogan B, Victorio D, Castellanos JG et al. IgA-coated E. Coli enriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation. Science Translational Medicine. 2017 Feb 8;9(376). eaaf9655. https://doi.org/10.1126/scitranslmed.aaf9655
Viladomiu, Monica ; Kivolowitz, Charles ; Abdulhamid, Ahmed ; Dogan, Belgin ; Victorio, Daniel ; Castellanos, Jim G. ; Woo, Viola ; Teng, Fei ; Tran, Nhan L. ; Sczesnak, Andrew ; Chai, Christina ; Kim, Myunghoo ; Diehl, Gretchen E. ; Ajami, Nadim J. ; Petrosino, Joseph F. ; Zhou, Xi K. ; Schwartzman, Sergio ; Mandl, Lisa A. ; Abramowitz, Meira ; Jacob, Vinita ; Bosworth, Brian ; Steinlauf, Adam ; Scherl, Ellen J. ; Wu, Hsin-Jung Joyce ; Simpson, Kenneth W. ; Longman, Randy S. / IgA-coated E. Coli enriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation. In: Science Translational Medicine. 2017 ; Vol. 9, No. 376.
@article{bcb4e749a2584f9bad5d341d029dcaed,
title = "IgA-coated E. Coli enriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation",
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.",
author = "Monica Viladomiu and Charles Kivolowitz and Ahmed Abdulhamid and Belgin Dogan and Daniel Victorio and Castellanos, {Jim G.} and Viola Woo and Fei Teng and Tran, {Nhan L.} and Andrew Sczesnak and Christina Chai and Myunghoo Kim and Diehl, {Gretchen E.} and Ajami, {Nadim J.} and Petrosino, {Joseph F.} and Zhou, {Xi K.} and Sergio Schwartzman and Mandl, {Lisa A.} and Meira Abramowitz and Vinita Jacob and Brian Bosworth and Adam Steinlauf and Scherl, {Ellen J.} and Wu, {Hsin-Jung Joyce} and Simpson, {Kenneth W.} and Longman, {Randy S.}",
year = "2017",
month = "2",
day = "8",
doi = "10.1126/scitranslmed.aaf9655",
language = "English (US)",
volume = "9",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "376",

}

TY - JOUR

T1 - IgA-coated E. Coli enriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation

AU - Viladomiu, Monica

AU - Kivolowitz, Charles

AU - Abdulhamid, Ahmed

AU - Dogan, Belgin

AU - Victorio, Daniel

AU - Castellanos, Jim G.

AU - Woo, Viola

AU - Teng, Fei

AU - Tran, Nhan L.

AU - Sczesnak, Andrew

AU - Chai, Christina

AU - Kim, Myunghoo

AU - Diehl, Gretchen E.

AU - Ajami, Nadim J.

AU - Petrosino, Joseph F.

AU - Zhou, Xi K.

AU - Schwartzman, Sergio

AU - Mandl, Lisa A.

AU - Abramowitz, Meira

AU - Jacob, Vinita

AU - Bosworth, Brian

AU - Steinlauf, Adam

AU - Scherl, Ellen J.

AU - Wu, Hsin-Jung Joyce

AU - Simpson, Kenneth W.

AU - Longman, Randy S.

PY - 2017/2/8

Y1 - 2017/2/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85012906125&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85012906125&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aaf9655

DO - 10.1126/scitranslmed.aaf9655

M3 - Article

VL - 9

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 376

M1 - eaaf9655

ER -