Gut Microbiota Perturbation in IgA Deficiency Is Influenced by IgA-Autoantibody Status
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Gut Microbiota Perturbation in IgA Deficiency Is Influenced by IgA-Autoantibody Status. / Moll, Janne Marie; Myers, Pernille Neve; Zhang, Chenchen; Eriksen, Carsten; Wolf, Johannes; Appelberg, K. Sofia; Lindberg, Greger; Bahl, Martin Iain; Zhao, Hui; Pan-Hammarström, Qiang; Cai, Kaiye; Jia, Huijue; Borte, Stephan; Nielsen, H. Bjørn; Kristiansen, Karsten; Brix, Susanne; Hammarström, Lennart.
In: Gastroenterology, Vol. 160, No. 7, 2021, p. 2423-2434.e5.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Gut Microbiota Perturbation in IgA Deficiency Is Influenced by IgA-Autoantibody Status
AU - Moll, Janne Marie
AU - Myers, Pernille Neve
AU - Zhang, Chenchen
AU - Eriksen, Carsten
AU - Wolf, Johannes
AU - Appelberg, K. Sofia
AU - Lindberg, Greger
AU - Bahl, Martin Iain
AU - Zhao, Hui
AU - Pan-Hammarström, Qiang
AU - Cai, Kaiye
AU - Jia, Huijue
AU - Borte, Stephan
AU - Nielsen, H. Bjørn
AU - Kristiansen, Karsten
AU - Brix, Susanne
AU - Hammarström, Lennart
N1 - Funding Information: Funding This research was supported by The Swedish Research Council (521-2014-2215) and Shenzhen Municipal Government of China (no. DRC-SZ [2015]162 and no. CXB201108250098A). Publisher Copyright: © 2021 AGA Institute
PY - 2021
Y1 - 2021
N2 - Background & Aims: IgA exerts its primary function at mucosal surfaces, where it binds microbial antigens to regulate bacterial growth and epithelial attachment. One third of individuals with IgA deficiency (IgAD) suffers from recurrent mucosal infections, possibly related to an altered microbiota. We aimed to delineate the impact of IgAD and the IgA-autoantibody status on the composition and functional capacity of the gut microbiota. Methods: We performed a paired, lifestyle-balanced analysis of the effect of IgA on the gut microbiota composition and functionality based on fecal samples from individuals with IgAD and IgA-sufficient household members (n = 100), involving quantitative shotgun metagenomics, species-centric functional annotation of gut bacteria, and strain-level analyses. We supplemented the data set with 32 individuals with IgAD and examined the influence of IgA-autoantibody status on the composition and functionality of the gut microbiota. Results: The gut microbiota of individuals with IgAD exhibited decreased richness and diversity and was enriched for bacterial species encoding pathogen-related functions including multidrug and antimicrobial peptide resistance, virulence factors, and type III and VI secretion systems. These functional changes were largely attributed to Escherichia coli but were independent of E coli strain variations and most prominent in individuals with IgAD with IgA-specific autoreactive antibodies. Conclusions: The microbiota of individuals with IgAD is enriched for species holding increased proinflammatory potential, thereby potentially decreasing the resistance to gut barrier–perturbing events. This phenotype is especially pronounced in individuals with IgAD with IgA-specific autoreactive antibodies, thus warranting a screening for IgA-specific autoreactive antibodies in IgAD to identify patients with IgAD with increased risk for gastrointestinal implications.
AB - Background & Aims: IgA exerts its primary function at mucosal surfaces, where it binds microbial antigens to regulate bacterial growth and epithelial attachment. One third of individuals with IgA deficiency (IgAD) suffers from recurrent mucosal infections, possibly related to an altered microbiota. We aimed to delineate the impact of IgAD and the IgA-autoantibody status on the composition and functional capacity of the gut microbiota. Methods: We performed a paired, lifestyle-balanced analysis of the effect of IgA on the gut microbiota composition and functionality based on fecal samples from individuals with IgAD and IgA-sufficient household members (n = 100), involving quantitative shotgun metagenomics, species-centric functional annotation of gut bacteria, and strain-level analyses. We supplemented the data set with 32 individuals with IgAD and examined the influence of IgA-autoantibody status on the composition and functionality of the gut microbiota. Results: The gut microbiota of individuals with IgAD exhibited decreased richness and diversity and was enriched for bacterial species encoding pathogen-related functions including multidrug and antimicrobial peptide resistance, virulence factors, and type III and VI secretion systems. These functional changes were largely attributed to Escherichia coli but were independent of E coli strain variations and most prominent in individuals with IgAD with IgA-specific autoreactive antibodies. Conclusions: The microbiota of individuals with IgAD is enriched for species holding increased proinflammatory potential, thereby potentially decreasing the resistance to gut barrier–perturbing events. This phenotype is especially pronounced in individuals with IgAD with IgA-specific autoreactive antibodies, thus warranting a screening for IgA-specific autoreactive antibodies in IgAD to identify patients with IgAD with increased risk for gastrointestinal implications.
KW - Autoimmunity
KW - Functional Profiling of the Gut Microbiota
KW - Immunoglobulin A
KW - Quantitative Metagenomics
KW - Strain-Level Analysis
U2 - 10.1053/j.gastro.2021.02.053
DO - 10.1053/j.gastro.2021.02.053
M3 - Journal article
C2 - 33662387
AN - SCOPUS:85106914108
VL - 160
SP - 2423-2434.e5
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 7
ER -
ID: 273756762