Immunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease

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...

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Veröffentlicht in:Cell 2014-08, Vol.158 (5), p.1000-1010
Hauptverfasser: Palm, Noah W., de Zoete, Marcel R., Cullen, Thomas W., Barry, Natasha A., Stefanowski, Jonathan, Hao, Liming, Degnan, Patrick H., Hu, Jianzhong, Peter, Inga, Zhang, Wei, Ruggiero, Elizabeth, Cho, Judy H., Goodman, Andrew L., Flavell, Richard A.
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •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 A method termed as immunoglobulin A coating can be applied to distinguish and potentially target bacteria that are potential drivers of inflammatory bowel disease from the remaining members of the microbiota.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2014.08.006