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Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease.

ABSTRACT: 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.

SUBMITTER: Palm NW

PROVIDER: S-EPMC4174347 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease.

Palm Noah W NW de Zoete Marcel R MR Cullen Thomas W TW Barry Natasha A NA Stefanowski Jonathan J Hao Liming L Degnan Patrick H PH Hu Jianzhong J Peter Inga I Zhang Wei W Ruggiero Elizabeth E Cho Judy H JH Goodman Andrew L AL Flavell Richard A RA

Cell 20140801 5

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 ...[more]

PMID: 25171403

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Project description:Background and aimsInflammatory bowel diseases (IBD) are considered to be dysregulated, immune-mediated disorders; and immunosuppressive medications are the mainstay of their treatment. Clinically, we have often observed low serum immunoglobulin (Ig) levels in these patients. The aim of this study was to assess the frequency and risk factors of secondary humoral immunodeficiency in IBD patients.MethodsWe conducted a cross-sectional study of eligible IBD patients with Crohn's disease (CD), ulcerative colitis (UC), indeterminate colitis (IC) or restorative proctocolectomy with ileal pouch, who having serum Ig measured. Demographic and clinical variables were measured. Univariate and multivariate analyses were performed.ResultsA total of 324 patients was included, with a mean age of 38.8 years and 158 (48.8%) being male. Low IgG, IgG1, IgA, and IgM were found in 22.7%, 23.4%, 7.9%, and 10.9% of patients, respectively. The shared risk factors for a low IgG or IgM level were increasing age [odds ratio (OR) = 1.13; 95% confidence interval (CI) 1.03-1.23 for low IgG level and OR = 1.33; 95% CI 1.15-1.56 for low IgM level] and hypoalbuminemia (OR = 1.83; 95% CI 1.01-3.33 for low IgG level and OR = 3.17; 95% CI 1.23-8.15 for low IgM level). In addition, thioprine use was associated with low IgA level (OR = 2.76; 95% CI 1.03-7.39). IBD disease duration was a risk factor for low IgG1 level (OR = 1.40; 95% CI 1.12-1.76). The presence of concurrent primary sclerosing cholangitis (OR = 0.064; 95% CI 0.007-0.60) and the use of biologics (OR = 0.16; 95% CI 0.033-0.79) were associated with normal IgG1 level. IgG level was lower in CD patients than that in UC/IC and ileal pouch patients (P = 0.042). IgG and IgA levels were elevated in patients with inflammatory conditions of the pouch (P = 0.01; P = 0.003, respectively).ConclusionsLow Ig level appears to be common in IBD patients. Increasing age, disease duration and hypoalbuminemia appeared to be risk factors. The findings may provide rationale for targeted therapy to boost humoral immunity in selected patients with IBD.

Dataset Information

Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease.

Publications

Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease.

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