Abstract

Immunoglobulin A Targets a Unique Subset of the Microbiota in Inflammatory Bowel Disease

Cell Host Microbe. 2020 Dec 31;S1931-3128(20)30665-X. doi: 10.1016/j.chom.2020.12.003.Online ahead of print.

Jason M Shapiro 1, Marcel R de Zoete 2, Noah W Palm 3, Yaro Laenen 2, Rene Bright 4, Meaghan Mallette 4, Kevin Bu 5, Agata A Bielecka 3, Fang Xu 6, Andres Hurtado-Lorenzo 7, Samir A Shah 8, Judy H Cho 9, Neal S LeLeiko 1, Bruce E Sands 10, Richard A Flavell 3, J C Clemente 11

 
     

Author information

  • 1Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Hasbro Children's Hospital, Providence, RI 02903, USA; Alpert Medical School of Brown University, Providence, RI 02903, USA.
  • 2Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • 3Human and Translational Immunobiology Program, Yale University School of Medicine, New Haven, CT 06519, USA.
  • 4Division of Gastroenterology, Rhode Island Hospital, Providence, RI 02903, USA.
  • 5Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • 6Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
  • 7Crohn's and Colitis Foundation, New York, NY 10017, USA.
  • 8Alpert Medical School of Brown University, Providence, RI 02903, USA; Division of Gastroenterology, Rhode Island Hospital, Providence, RI 02903, USA.
  • 9Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • 10Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • 11Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: jose.clemente@mssm.edu.

Abstract

The immunopathogenesis of inflammatory bowel disease (IBD) has been attributed to a combination of host genetics and intestinal dysbiosis. Previous work in a small cohort of IBD patients suggested that pro-inflammatory bacterial taxa are highly coated with secretory immunoglobulin IgA. Using bacterial fluorescence-activated cell sorting coupled with 16S rRNA gene sequencing (IgA-SEQ), we profiled IgA coating of intestinal microbiota in a large cohort of IBD patients and identified bacteria associated with disease and treatment. Forty-three bacterial taxa displayed significantly higher IgA coating in IBD compared with controls, including 8 taxa exhibiting differential IgA coating but similar relative abundance. Patients treated with anti-TNF-α therapies exhibited dramatically altered microbiota-specific IgA responses compared with controls. Furthermore, increased IgA coating of Oscillospira was associated with a delay in time to surgery. These results demonstrate that investigating IgA responses to microbiota can uncover potential disease-modifying taxa and reveal improved biomarkers of clinical course in IBD.

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