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 -