Abstract
Immunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) in humans is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that mucosal secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and taxa-specific antibody coating of the gut microbiota in 15 sIgAd subjects and matched controls. Despite the secretion of compensatory IgM into the gut lumen, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls. These alterations were characterized by a trend towards decreased overall microbial diversity as well as significant shifts in the relative abundances of specific microbial taxa. While secretory IgA in healthy controls targeted a defined subset of the microbiota via high-level coating, compensatory IgM in sIgAd subjects showed less specificity than IgA and bound a broader subset of the microbiota. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community.
Highlights
Secretory immunoglobulin A is the dominant antibody isotype in mucosal secretions and plays an essential role in defense against pathogenic microorganisms[1]
To identify which specific taxa were targeted by IgA or IgM, we compared the taxonomic compositions of the Ig-coated versus non-coated fractions in IgA-deficient subjects and controls using Linear Discriminant Analysis Effect Size (LEfSe) (Fig. 3c,d). These analyses revealed that Haemophilus other, Slackia spp and an UC Enterobacteriaceae were significantly IgA coated in healthy controls, though none of these differences were statistically significant after false discovery rate (FDR) correction (Fig. 3c,e, Supplementary Table 2)
Immunoglobulin A is best known for its role in protecting against infections at mucosal surfaces; it has recently become clear that IgA plays a critical role in shaping the composition and function of the gut microbiota in mice
Summary
Secretory immunoglobulin A is the dominant antibody isotype in mucosal secretions and plays an essential role in defense against pathogenic microorganisms[1]. Even in the absence of infection, the body produces approximately four grams of IgA daily, more than all other antibody isotypes combined[2] Much of this IgA is secreted into the intestinal lumen, where it binds to and ‘coats’ specific members of the gut microbiota—the trillions of bacteria that constitutively colonize the human intestinal tract[3]. Secretory IgA plays a crucial role in shaping the composition and function of the gut microbiota in mice[4,5]. Compensatory secreted IgM in IgA-deficient subjects displays distinct microbial binding patterns as compared to conventional secretory IgA. Together, these studies reveal a unique and non-redundant role for secretory IgA in shaping gut microbial community structure in humans
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