Immunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease

Cell. 2014 Aug 28;158(5):1000-1010. doi: 10.1016/j.cell.2014.08.006.

Abstract

Specific members of the intestinal microbiota dramatically affect inflammatory bowel disease (IBD) in mice. In humans, however, identifying bacteria that preferentially affect disease susceptibility and severity remains a major challenge. Here, we used flow-cytometry-based bacterial cell sorting and 16S sequencing to characterize taxa-specific coating of the intestinal microbiota with immunoglobulin A (IgA-SEQ) and show that high IgA coating uniquely identifies colitogenic intestinal bacteria in a mouse model of microbiota-driven colitis. We then used IgA-SEQ and extensive anaerobic culturing of fecal bacteria from IBD patients to create personalized disease-associated gut microbiota culture collections with predefined levels of IgA coating. Using these collections, we found that intestinal bacteria selected on the basis of high coating with IgA conferred dramatic susceptibility to colitis in germ-free mice. Thus, our studies suggest that IgA coating identifies inflammatory commensals that preferentially drive intestinal disease. Targeted elimination of such bacteria may reduce, reverse, or even prevent disease development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis, Ulcerative / immunology*
  • Colitis, Ulcerative / microbiology
  • Colitis, Ulcerative / pathology
  • Crohn Disease / immunology*
  • Crohn Disease / microbiology
  • Crohn Disease / pathology
  • DNA, Bacterial / analysis
  • Dysbiosis / immunology
  • Dysbiosis / microbiology
  • Humans
  • Immunoglobulin A / immunology*
  • Inflammasomes / immunology
  • Inflammation / immunology
  • Inflammation / microbiology
  • Intestines / immunology
  • Intestines / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Microbiota*
  • RNA, Ribosomal, 16S / analysis
  • Specific Pathogen-Free Organisms

Substances

  • DNA, Bacterial
  • Immunoglobulin A
  • Inflammasomes
  • RNA, Ribosomal, 16S