title: 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.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Noah W
authors.initials: NW
authors.lastname: Palm
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06510, USA.
authors.forename: Marcel R
authors.initials: MR
authors.lastname: de Zoete
authors.affiliation: Microbial Diversity Institute and Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Cullen
authors.affiliation: Microbial Diversity Institute and Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Barry
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stefanowski
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Liming
authors.initials: L
authors.lastname: Hao
authors.affiliation: Microbial Diversity Institute and Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Degnan
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Inga
authors.initials: I
authors.lastname: Peter
authors.affiliation: Departments of Medicine and Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Departments of Medicine and Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ruggiero
authors.affiliation: Departments of Medicine and Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Judy H
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Microbial Diversity Institute and Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Goodman
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06510, USA. Electronic address: richard.flavell@yale.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004269:DNA, Bacterial / Q000032:analysis; D064806:Dysbiosis / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D058847:Inflammasomes / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D013047:Specific Pathogen-Free Organisms
chemical_list: D004269:DNA, Bacterial; D007070:Immunoglobulin A; D058847:Inflammasomes; D012336:RNA, Ribosomal, 16S