Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease

By Noah W. Palm, Marcel R. de Zoete, T. W. Cullen, N. Barry, Jonathan Stefanowski, L. Hao, P. Degnan, Jianzhong Hu, I. Peter, Wei Zhang and 4 more. Cell, 2014

841 citations recorded by the source corpus.

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 pre-defined 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.

Subfields: Gastroenterology, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/942cd2075a659442cd7a001d6d194bc93cf854ba

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Gastroenterology

1. K. Honda

In Infectious Diseases

1. G. Núñez
2. K. Honda
3. Y. Umesaki
4. I. Ivanov
5. Eran Elinav
6. Y. Belkaid

In Molecular Biology

1. K. Honda
2. G. Núñez
3. Y. Umesaki
4. I. Ivanov
5. D. Zheng
6. Eran Elinav
7. Y. Belkaid

Citations in the corpus

• New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD (2019, background): “(B) Defective autophagy leads to intestinal dysbiosis and increased IgA-coated bacterial amount [26,27,32].”
• Interaction between microbiota and immunity in health and disease (2020, background): “Interestingly, intestinal secretory IgA antibodies preferentially coat colitogenic bacteria, therefore preventing perturbation of enteric homeostasis and inflammation.(102) In the absence of B cells, or of IgA, intestinal epithelia upregulate epithelium-inherent immune defense mechanisms mediated by”
• Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells (2015, positive): “Th17 cells induce the recruitment of neutrophils and activation of ECs, leading to enhanced clearance of extracellular pathogens in concert with other immune cells such as IgA-secreting plasma cells and group 3 innate lymphoid cells (ILC3s).”