Abstract

Bridging the Gap Between Host Immune Response and Intestinal Dysbiosis in Inflammatory Bowel Disease: Does IgA Mark the Spot?

Shapiro JM1, Cho JH2, Sands BE2, LeLeiko NS3. Clin Gastroenterol Hepatol. 2015 Feb 25. pii: S1542-3565(15)00167-6. doi: 10.1016/j.cgh.2015.02.028. [Epub ahead of print]
 
     
Author information

1Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Department of Pediatrics, Hasbro Children's Hospital/Rhode Island Hospital, Providence, Rhode Island; The Warren Alpert School of Medicine at Brown University, Providence, Rhode Island. Electronic address: jshapiro@lifespan.org. 2Icahn School of Medicine at Mount Sinai, Dr. Henry D. Janowitz Division of Gastroenterology, New York, New York. 3Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Department of Pediatrics, Hasbro Children's Hospital/Rhode Island Hospital, Providence, Rhode Island; The Warren Alpert School of Medicine at Brown University, Providence, Rhode Island.

Abstract

Inflammatory bowel disease (IBD) is a chronic, debilitating condition characterized by relapsing and remitting episodes of gastrointestinal inflammation. As the incidence and prevalence have increased, so has our understanding of the pathophysiology of this complex, immunologically-mediated disease. With advances in bacterial and human gene sequencing technologies, a significant amount of work has focused on how alterations in the intestinal microbiome affect disease onset and progression. A recent study in Cell suggests that it may be possible to identify specific bacteria responsible for promoting a pro-inflammatory state by assessing the degree to which they are coated by the immunoglobulin, IgA. A combination of antibody-based bacterial cell sorting, flow cytometry and 16s ribosomal RNA gene sequencing was used to identify IgA-coated bacteria from stool of specific pathogen-free (SPF) mice. This technique was used to demonstrate that IgA-coated bacteria were indeed detectable and increased in a mouse model of colitis. Stool from patients with IBD was then used to generate two groups of IgA+ and IgA- bacterial consortia. When transplanted into SPF mice, no initial clinical differences were noted. However, when mice with dextran sodium sulfate induced colitis were transplanted with the IgA+ bacterial strains they exhibited severe exacerbation of intestinal inflammation while the IgA- group developed minimal symptoms. These findings suggest that bacteria highly coated with IgA are potentially responsible for driving gut inflammation in patients with IBD. These results may represent a critical advance in our understanding of the complex interactions between the host immune system and commensal microorganisms as it relates to the development and disease course of IBD. Future work will focus on how these findings can be translated into the development of individualized, microbiota-specific therapies.

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