Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases

Abstract Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse‐transcytosis, the apical‐to‐basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microb...

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Main Authors: Eva Michaud, Louis Waeckel, Rémi Gayet, Roman Goguyer‐Deschaumes, Blandine Chanut, Fabienne Jospin, Katell Bathany, Magali Monnoye, Coraline Genet, Amelie Prier, Caroline Tokarski, Philippe Gérard, Xavier Roblin, Nicolas Rochereau, Stéphane Paul
Format: Article
Language:English
Published: Springer Nature 2022-07-01
Series:EMBO Molecular Medicine
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Online Access:https://doi.org/10.15252/emmm.202115386
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author Eva Michaud
Louis Waeckel
Rémi Gayet
Roman Goguyer‐Deschaumes
Blandine Chanut
Fabienne Jospin
Katell Bathany
Magali Monnoye
Coraline Genet
Amelie Prier
Caroline Tokarski
Philippe Gérard
Xavier Roblin
Nicolas Rochereau
Stéphane Paul
author_facet Eva Michaud
Louis Waeckel
Rémi Gayet
Roman Goguyer‐Deschaumes
Blandine Chanut
Fabienne Jospin
Katell Bathany
Magali Monnoye
Coraline Genet
Amelie Prier
Caroline Tokarski
Philippe Gérard
Xavier Roblin
Nicolas Rochereau
Stéphane Paul
author_sort Eva Michaud
collection DOAJ
description Abstract Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse‐transcytosis, the apical‐to‐basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan–glycan interaction. Here, we asked whether IgA1 and IgA2‐microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC‐purified IgA, we show that reverse‐transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA‐bound microbiota in CD and UC showed distinct IgA1‐ and IgA2‐associated microbiota; the IgA1+ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti‐glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis.
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spelling doaj-art-412ce5dad93d49a68a3f2f1a2bf9f5602025-08-20T03:46:29ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-07-0114812110.15252/emmm.202115386Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseasesEva Michaud0Louis Waeckel1Rémi Gayet2Roman Goguyer‐Deschaumes3Blandine Chanut4Fabienne Jospin5Katell Bathany6Magali Monnoye7Coraline Genet8Amelie Prier9Caroline Tokarski10Philippe Gérard11Xavier Roblin12Nicolas Rochereau13Stéphane Paul14CIRI – Centre International de Recherche en Infectiologie, Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308CIRI – Centre International de Recherche en Infectiologie, Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308CIRI – Centre International de Recherche en Infectiologie, Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308CIRI – Centre International de Recherche en Infectiologie, Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308CIRI – Centre International de Recherche en Infectiologie, Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308CIRI – Centre International de Recherche en Infectiologie, Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308Chimie et Biologie des Membranes et des Nano‐objets (UMR 5248), Université de Bordeaux, CNRS, Bordeaux INPMicalis Institute, INRAE, AgroParisTech, Université Paris‐SaclayInserm UMR 1098 Right, Université Bourgogne Franche‐ComtéCIRI – Centre International de Recherche en Infectiologie, Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308Chimie et Biologie des Membranes et des Nano‐objets (UMR 5248), Université de Bordeaux, CNRS, Bordeaux INPMicalis Institute, INRAE, AgroParisTech, Université Paris‐SaclayCIRI – Centre International de Recherche en Infectiologie, Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308CIRI – Centre International de Recherche en Infectiologie, Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308CIRI – Centre International de Recherche en Infectiologie, Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308Abstract Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse‐transcytosis, the apical‐to‐basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan–glycan interaction. Here, we asked whether IgA1 and IgA2‐microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC‐purified IgA, we show that reverse‐transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA‐bound microbiota in CD and UC showed distinct IgA1‐ and IgA2‐associated microbiota; the IgA1+ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti‐glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis.https://doi.org/10.15252/emmm.202115386SIgAmicrobiotaglycosylationIBDimmunity
spellingShingle Eva Michaud
Louis Waeckel
Rémi Gayet
Roman Goguyer‐Deschaumes
Blandine Chanut
Fabienne Jospin
Katell Bathany
Magali Monnoye
Coraline Genet
Amelie Prier
Caroline Tokarski
Philippe Gérard
Xavier Roblin
Nicolas Rochereau
Stéphane Paul
Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases
EMBO Molecular Medicine
SIgA
microbiota
glycosylation
IBD
immunity
title Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases
title_full Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases
title_fullStr Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases
title_full_unstemmed Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases
title_short Alteration of microbiota antibody‐mediated immune selection contributes to dysbiosis in inflammatory bowel diseases
title_sort alteration of microbiota antibody mediated immune selection contributes to dysbiosis in inflammatory bowel diseases
topic SIgA
microbiota
glycosylation
IBD
immunity
url https://doi.org/10.15252/emmm.202115386
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