Minimal Variation of Human Oral Virome and Microbiome in IgA Deficiency Challenges an Irreplaceable IgA Role for Shaping Oral Commensal Microbiota

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 on both the human virome and microbiome. Unexpectedly, metagenomic and experimental data in human IgA deficiency 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 (2-fold) of bacterial cells (p-value < 0.01) and viruses was observed in IgA-deficiency. Our results challenge the view of an irreplaceable IgA role for regulating the composition and function of our commensal microbiota and pose the question whether other “back-up” Ig-independent mechanisms might exist for maintaining a functional commensal microbiome.