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

Cell Host Microbe. 2021 Jan 13;29(1):83-93.e3. doi: 10.1016/j.chom.2020.12.003. Epub 2021 Jan 1.

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.

Keywords: Crohn’s disease; dysbiosis; immunoglobulin A; inflammatory bowel disease; microbiome; ulcerative colitis.

MeSH terms

  • Adult
  • Bacteria / growth & development
  • Bacteria / immunology*
  • Clostridiales / growth & development
  • Clostridiales / immunology
  • Cohort Studies
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / microbiology
  • Colitis, Ulcerative / physiopathology
  • Crohn Disease / drug therapy
  • Crohn Disease / immunology
  • Crohn Disease / microbiology
  • Crohn Disease / physiopathology
  • Disease Progression
  • Female
  • Gastrointestinal Microbiome / immunology*
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Immunoglobulin A, Secretory / immunology*
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / microbiology*
  • Inflammatory Bowel Diseases / physiopathology
  • Male
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Immunoglobulin A, Secretory
  • Tumor Necrosis Factor-alpha