Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease

Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J, Hao L, Degnan PH, Hu J, Peter I, Zhang W, Ruggiero E, Cho JH, Goodman AL, and Flavell RA.

Cell 2014 Aug 28;158(5):1000-10

Speaker: Chih-Yu Huang (黃智裕)               Time: 13:00~14:00, Dec 31,2014

Commentator: Dr. I-Hsiu Huang (黃一修老師)     Place: Room 601

Abstract:

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, induces inappropriate immune response to intestinal microbiota in genetically susceptible hosts^[1].However, it is still challenging to identify which specific colitogenic bacteria induce the inflammatory responses in IBD patients. The author hypothesized the assay of IgA coating to the specific pathogenic bacteria combing with 16S sequencing (IgA-SEQ) could successfully identify colitogenic bacteria. Using IgA-SEQ, they revealed that colitogenic bacteria were highly coated with IgA in the mouse model of microbiota driven colitis. Additionally, highly IgA-coated members of gut microbiota were also identified in IBD patients. Next, the author evaluated the effects of IgA-positive and IgA-negative intestinal microbiota by establishing a gnotobiotic mouse model and showed that the bacteria isolated from IBD patients could also induce strong IgA coating in the individualized gnotobiotic mice. Furthermore, the gnotobiotic mice enriched with IgA-positive microbiota also demonstrated severe intestinal inflammation, significant shortening of the colon, increased cellular infiltration, and loss of colon integrity after the induction of colitis with dextran sodium sulfate. In conclusion, IgA-SEQ can identify the highly IgA-coated colitogenic bacteria in IBD patients, and the isolated microbiota were able to induce severe intestinal inflammation in the mouse model of IBD. Elimination of the specific microbiota may ameliorate or prevent disease development.

Reference:

1.     Abraham C, and Cho JH. Inflammatory Bowel Disease N Engl J Med 2009;361:2066-78.