Cell Host Microbe. 2020 Dec 31;S1931-3128(20)30665-X. doi: 10.1016/j.chom.2020.12.003.Online ahead of print.

Jason M Shapiro ¹, Marcel R de Zoete ², Noah W Palm ³, Yaro Laenen ², Rene Bright ⁴, Meaghan Mallette ⁴, Kevin Bu ⁵, Agata A Bielecka ³, Fang Xu ⁶, Andres Hurtado-Lorenzo ⁷, Samir A Shah ⁸, Judy H Cho ⁹, Neal S LeLeiko ¹, Bruce E Sands ¹⁰, Richard A Flavell ³, J C Clemente ¹¹

Author information

• ¹Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Hasbro Children's Hospital, Providence, RI 02903, USA; Alpert Medical School of Brown University, Providence, RI 02903, USA.
• ²Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
• ³Human and Translational Immunobiology Program, Yale University School of Medicine, New Haven, CT 06519, USA.
• ⁴Division of Gastroenterology, Rhode Island Hospital, Providence, RI 02903, USA.
• ⁵Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
• ⁶Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
• ⁷Crohn's and Colitis Foundation, New York, NY 10017, USA.
• ⁸Alpert Medical School of Brown University, Providence, RI 02903, USA; Division of Gastroenterology, Rhode Island Hospital, Providence, RI 02903, USA.
• ⁹Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
• ¹⁰Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
• ¹¹Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: jose.clemente@mssm.edu.

Abstract

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.