title: Intestinal IgA as a modulator of the gut microbiota.
abstract: Accumulating evidence suggests that dysbiosis plays a role in the pathogenesis of intestinal diseases including inflammatory bowel disease (IBD) as well as extra-intestinal disorders. As a modulator of the intestinal microbiota, we isolated a mouse monoclonal IgA antibody (clone W27) with high affinities for multiple commensal bacteria, but not for beneficial bacteria such as Lactobacillus casei (L. casei). Via specific recognition of an epitope in serine hydroxymethyltransferase (SHMT), a bacterial metabolic enzyme, W27 IgA selectively inhibited the in vitro growth of bound bacteria, including Escherichia coli (E. coli), while having no effect on unbound beneficial bacteria such as L. casei. By modulating the gut microbiota in vivo, oral administration of W27 IgA effectively prevented development of colitis in several mouse models. Here we discuss how intestinal IgA modulates the gut microbiota through recognition of SHMT.
authors.affiliation: a Applied Immunology , Nara Institute of Science and Technology , Nara , Japan.
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Okai
authors.affiliation: a Applied Immunology , Nara Institute of Science and Technology , Nara , Japan.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Usui
authors.affiliation: a Applied Immunology , Nara Institute of Science and Technology , Nara , Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Ohta
authors.affiliation: b Center for Information Biology , National Institute of Genetics , Shizuoka , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
authors.affiliation: b Center for Information Biology , National Institute of Genetics , Shizuoka , Japan.
authors.forename: Ken
authors.identifier: 0000-0001-8662-9958
authors.initials: K
authors.lastname: Kurokawa
authors.affiliation: c Yakult Central Institute , Tokyo , Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: d RIKEN Center for Integrative Medical Sciences (IMS) , Kanagawa , Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kato
authors.affiliation: d RIKEN Center for Integrative Medical Sciences (IMS) , Kanagawa , Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyauchi
authors.affiliation: d RIKEN Center for Integrative Medical Sciences (IMS) , Kanagawa , Japan.|e Graduate School of Medicine , Chiba University , Chiba , Japan.|f Graduate School of Medical Life Science , Yokohama City University , Kanagawa , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohno
authors.affiliation: a Applied Immunology , Nara Institute of Science and Technology , Nara , Japan.|g PRESTO, Japan Science and Technology Agency , Saitama , Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Shinkura
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000907:Antibodies, Bacterial / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000382:microbiology*; D012696:Glycine Hydroxymethyltransferase / Q000276:immunology; D006131:Growth Inhibitors / Q000008:administration & dosage; D007070:Immunoglobulin A / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D051379:Mice
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D006131:Growth Inhibitors; D007070:Immunoglobulin A; D007155:Immunologic Factors; D012696:Glycine Hydroxymethyltransferase
keywords: AID; IgA; dysbiosis; gut microbiota; inflammatory bowel disease; monoclonal antibody