Abstract
Immunoglobulin A (IgA) is the dominant antibody found in our mucosal secretions and has long been recognized to play an important role in protecting our epithelium from pathogens. Recently, IgA has been shown to be involved in gut homeostatic regulation by ‘recognizing’ and shaping our commensal microbes. Paradoxically, yet selective IgA-deficiency is often described as asymptomatic and there is a paucity of studies only focused on the mice and human gut microbiome context fully ignoring other niches of our body and our commensal viruses. Here, we used as a model the human oral cavity and employed a holistic view and studied the impact of IgA deficiency and also common variable IgA and IgM immunodeficiencies (CVID), on both the human virome and microbiome. Unexpectedly, metagenomic and experimental data in human IgA deficiency and CVID indicate minimal-moderate changes in microbiome and virome composition compared to healthy control group and point out to a rather functional, resilient oral commensal viruses and microbes. However, a significant depletion (two fold) of bacterial cells (p-value < 0.01) and viruses was observed in IgA-deficiency. Our results demonstrate that, within the limits of our cohort, IgA role is not critical for maintaining a rather functional salivary microbiome and suggest that IgA is not a major influence on the composition of abundant commensal microbes.
Highlights
Immunoglobulin A (IgA) is the dominant antibody found in our mucosal secretions and has long been recognized to play an important role in protecting our epithelium from pathogens
We collected saliva samples from 26 volunteers (16 healthy controls, 7 IgA-deficient patients and 3 with common variable immunodeficiency (CVID) lacking IgA and with altered levels of IgM; in some cases, undetectable) that were processed for 16S rRNA gene Illumina sequencing (Table S1), viral and microbial metagenomics and fluorescence microscopy (Fig. S1)
Clinical data and written consent were obtained from all patients. 16S rRNA gene Illumina sequencing data using amplicon sequence variants (ASV) demonstrated that all common commensalistic oral[16] bacterial genera (e.g. Streptococcus, Prevotella and Pasteurella) were predominant in all samples including IgA-deficiency and common variable IgA and IgM immunodeficiencies (CVID) samples (≥ 80% of total bacterial community, Fig. 1A)
Summary
Immunoglobulin A (IgA) is the dominant antibody found in our mucosal secretions and has long been recognized to play an important role in protecting our epithelium from pathogens. It has been proposed that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis and commensal gut microbes use this antibody for mucosal colonization[8] These studies and others (see a recent comprehensive review by Pabst and Slack3) have broadened our view and point that IgA seems to play a role shaping commensal microbiome and maintaining an adequate equilibrium on host-microbiome s ymbiosis[7,8,9,10]. Paraphrasing a recent review by Pabst and Slack3, ‘IgA is a divisive molecule and this Odyssey seems particular confusing’ To address these questions, we analyzed and discussed the impact of IgA deficiency on the oral microbiome employing a more holistic view considering in our microbiome study the viral community s tructure[13,14] along with changes in microbial abundance (viruses and bacteria) between control and IgA deficiency groups
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