Immunoglobulin A Targets a Unique Subset of the Microbiota in Inflammatory Bowel Disease

• Published in: Cell host & microbe 2021-01, Vol.29 (1), p.83-93.e3
• Main Authors: Shapiro, Jason M., de Zoete, Marcel R., Palm, Noah W., Laenen, Yaro, Bright, Rene, Mallette, Meaghan, Bu, Kevin, Bielecka, Agata A., Xu, Fang, Hurtado-Lorenzo, Andres, Shah, Samir A., Cho, Judy H., LeLeiko, Neal S., Sands, Bruce E., Flavell, Richard A., Clemente, J.C.
• Format: Article
• Language: English
• Subjects: Crohn’s disease; dysbiosis; immunoglobulin A; inflammatory bowel disease; microbiome; ulcerative colitis
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2020.12.003

The immunopathogenesis of inflammatory bowel disease (IBD) has been attributed to a combination of host genetics and intestinal dysbiosis. Previous work in a small cohort of IBD patients suggested that pro-inflammatory bacterial taxa are highly coated with secretory immunoglobulin IgA. Using bacterial fluorescence-activated cell sorting coupled with 16S rRNA gene sequencing (IgA-SEQ), we profiled IgA coating of intestinal microbiota in a large cohort of IBD patients and identified bacteria associated with disease and treatment. Forty-three bacterial taxa displayed significantly higher IgA coating in IBD compared with controls, including 8 taxa exhibiting differential IgA coating but similar relative abundance. Patients treated with anti-TNF-α therapies exhibited dramatically altered microbiota-specific IgA responses compared with controls. Furthermore, increased IgA coating of Oscillospira was associated with a delay in time to surgery. These results demonstrate that investigating IgA responses to microbiota can uncover potential disease-modifying taxa and reveal improved biomarkers of clinical course in IBD. [Display omitted] •IgA-coated bacteria were evaluated in a large cohort of IBD patients using IgA-SEQ•IgA-SEQ identified distinct IBD-associated bacteria compared with the relative abundance•Anti-TNFα treated patients exhibited altered microbiota-specific IgA responses•IgA coating of Oscillospira was associated with a delay in time to surgery in IBD Shapiro et al. explored patterns of secretory IgA-coated bacteria in a cohort of patients with inflammatory bowel disease (IBD). Medications, specifically TNFα inhibitors, had a notable impact on microbiota-specific IgA responses. IgA coating of Oscillospira was associated with a delay in surgery. IgA-SEQ may serve as a biomarker in IBD.