Cell
Volume 158, Issue 5, 28 August 2014, Pages 1000-1010
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Article
Immunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease

https://doi.org/10.1016/j.cell.2014.08.006Get rights and content
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Highlights

  • Bacterial members of the intestinal microbiota are differentially coated with IgA

  • A limited number of intestinal bacterial species are highly coated with IgA

  • IgA coating defines a subset of bacteria that selectively stimulates intestinal immunity

  • High IgA coating marks colitogenic bacteria in inflammatory bowel disease

Summary

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.

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Co-first author

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Present address: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA

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Present address: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA