IgA in human health and diseases: Potential regulator of commensal microbiota

Abstract

Gut microbiota has extensive and tremendous impacts on human physiology and pathology. The regulation of microbiota is therefore a cardinal problem for the mutualistic relationship, as both microbial overgrowth and excessive immune reactions toward them could potentially be detrimental to host homeostasis. Growing evidence suggests that IgA, the most dominant secretory immunoglobulin in the intestine, regulates the colonization of commensal microbiota, and consequently, the microbiota-mediated intestinal and extra-intestinal diseases. In this review, we discuss the interactions between IgA and gut microbiota particularly relevant to human pathophysiology. We review current knowledge about how IgA regulates gut microbiota in humans and about the molecular mechanisms behind this interaction. We further discuss the potential role of IgA in regulating human diseases by extrapolating experimental findings, suggesting that IgA can be a future therapeutic strategy that functionally modulates gut microbiota.

Keywords: adaptive immunity; gut microbiota; human immunology; immunoglobulin A; microbial metabolite.

Figure 1

The gut microbiota and their small molecules. The gut microbiota possesses millions of genes and produces thousands of small molecules. Here we summarized representative microbe-derived small molecules, including organic acids, amino acids and their derivatives, vitamins, secondary bile acids, and lipids. SCFAs, short-chain fatty acids; BCAA, branched-chain amino acids; GABA, gamma-aminobutyric acid.

Figure 2

Potential application of IgA to human diseases. IgA-oriented therapies that modulate the gut microbiota could be utilized to control disease susceptibility. First, prebiotics (e.g., dietary fiber) and probiotics increase intestinal IgA production and modulate IgA-coating bacteria. In turn, IgA-coated Lactobacillus could be isolated and harnessed as a probiotic strain that directly interacts with the mucus layer and epithelial cells. Although these methods are relatively easy to implement, their effects on the intestinal immune system are not specific to IgA production. In addition, it is difficult to induce IgA reactive with specific microbes of interest. By contrast, vaccination and monoclonal IgA administration are more sophisticated in the sense that these methods leverage “specificity” toward certain microbes, a cardinal feature of adaptive immunity. As the efficacy of these methods has been shown in mouse models (e.g., colitis and high-fat diet-induced obesity), these approaches that target specific microbes of interest would be promising.