Bridging the gap between host immune response and intestinal dysbiosis in inflammatory bowel disease: does immunoglobulin A mark the spot?
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 proinflammatory state by assessing the degree to which they are coated by the immunoglobulin (Ig) A. 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 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 2 groups of IgA+ and IgA- bacterial consortia. When transplanted into specific pathogen-free 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, whereas 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.
Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Department of Pediatrics, Hasbro Children's Hospital/Rhode Island Hospital, Providence, Rhode Island; Warren Alpert School of Medicine at Brown University, Providence, Rhode Island. Electronic address: jshapiro@lifespan.org.
Jason M
JM
Shapiro
Icahn School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, New York.
Judy H
JH
Cho
Icahn School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, New York.
Bruce E
BE
Sands
Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Department of Pediatrics, Hasbro Children's Hospital/Rhode Island Hospital, Providence, Rhode Island; Warren Alpert School of Medicine at Brown University, Providence, Rhode Island.
Neal S
NS
LeLeiko
D000818:Animals; D064806:Dysbiosis; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D051379:Mice
D007070:Immunoglobulin A
Dysbiosis; Immunoglobulin A; Inflammatory Bowel Disease; Microbiome