@article{e377e8e4cb9043d6aa010dbd12a9170a,
title = "Immunoglobulin A Targets a Unique Subset of the Microbiota in Inflammatory Bowel Disease",
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.",
keywords = "Crohn's disease, dysbiosis, immunoglobulin A, inflammatory bowel disease, microbiome, ulcerative colitis",
author = "Shapiro, \{Jason M\} and \{de Zoete\}, \{Marcel R\} and Palm, \{Noah W\} and Yaro Laenen and Rene Bright and Meaghan Mallette and Kevin Bu and Bielecka, \{Agata A\} and Fang Xu and Andres Hurtado-Lorenzo and Shah, \{Samir A\} and Cho, \{Judy H\} and LeLeiko, \{Neal S\} and Sands, \{Bruce E\} and Flavell, \{Richard A\} and Clemente, \{J C\}",
note = "Funding Information: J.M.S. was supported by a COBRE Immune Based Interventions Against Infectious Diseases Pilot grant (P20 GM104317). M.R.dZ. was supported by a VIDI grant from the Netherlands Organization for Scientific Research (NWO, grant 91715377) and the Utrecht exposome Hub of Utrecht Life Sciences (www.uu.nl/exposome), funded by the Executive Board of Utrecht University. J.H.C. was supported by a grant from NIH NIDDK (U01 DK062422). J.C.C. was partially supported by a grant from NIH NIDDK (5R01DK114038). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. J.M.S. M.R.d.Z. N.W.P. and J.C.C. conceived and designed the study and wrote the manuscript. M.R.d.Z. N.W.P. Y.L. and A.A.B. performed all experiments. J.C.C. and K.B. curated and analyzed data. J.M.S. R.B. M.M. S.S. N.S.L. and B.E.S. enrolled patients, maintained clinical dataset, and collected samples. A.H.L. F.X. J.H.C. N.S.L. B.E.S. and R.A.F. supervised research, assisted with experimental design, and co-wrote the manuscript. N.W.P. M.R.d.Z. and R.A.F. are co-founders of, consultants for, and hold equity in Artizan Biosciences. N.W.P. M.R.d.Z. and R.A.F. are inventors on a patent application for IgA-SEQ. Funding Information: J.M.S. was supported by a COBRE Immune Based Interventions Against Infectious Diseases Pilot grant ( P20 GM104317 ). M.R.dZ. was supported by a VIDI grant from the Netherlands Organization for Scientific Research (NWO, grant 91715377 ) and the Utrecht exposome Hub of Utrecht Life Sciences ( www.uu.nl/exposome ), funded by the Executive Board of Utrecht University . J.H.C. was supported by a grant from NIH NIDDK ( U01 DK062422 ). J.C.C. was partially supported by a grant from NIH NIDDK ( 5R01DK114038 ). Publisher Copyright: {\textcopyright} 2020",
year = "2021",
month = jan,
day = "13",
doi = "10.1016/j.chom.2020.12.003",
language = "English",
volume = "29",
pages = "83--93.e3",
journal = "Cell Host \& Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "1",
}