Carotenoid supplementation and retinoic acid in immunoglobulin A regulation of the gut microbiota dysbiosis

Abstract

Dysbiosis, a broad spectrum of imbalance of the gut microbiota, may progress to microbiota dysfunction. Dysbiosis is linked to some human diseases, such as inflammation-related disorders and metabolic syndromes. However, the underlying mechanisms of the pathogenesis of dysbiosis remain elusive. Recent findings suggest that the microbiome and gut immune responses, like immunoglobulin A production, play critical roles in the gut homeostasis and function, and the progression of dysbiosis. In the past two decades, much progress has been made in better understanding of production of immunoglobulin A and its association with commensal microbiota. The present minireview summarizes the recent findings in the gut microbiota dysbiosis and dysfunction of immunoglobulin A induced by the imbalance of pathogenic bacteria and commensal microbiota. We also propose the potentials of dietary carotenoids, such as β-carotene and astaxanthin, in the improvement of the gut immune system maturation and immunoglobulin A production, and the consequent promotion of the gut health. Impact statement The concept of carotenoid metabolism in the gut health has not been well established in the literature. Here, we review and discuss the roles of retinoic acid and carotenoids, including pro-vitamin A carotenoids and xanthophylls in the maturation of the gut immune system and IgA production. This is the first review article about the carotenoid supplements and the metabolites in the regulation of the gut microbiome. We hope this review would provide a new direction for the management of the gut microbiota dysbiosis by application of bioactive carotenoids and the metabolites.

Keywords: Astaxanthin; beta-carotene oxygenase 2; gut microbiome; immune system; vitamin A.

Figure 1.

The phylum-level changes of the cecal microbiota in BCO2 knockout (KO) and the wild-type (WT) mice after administration of 0.04% astaxanthin (w/w). Six-week-old mice were fed either the control (AIN-93M) or astaxanthin (ASTX, AIM-93M supplemented with 0.04% astaxanthin (w/w)) diet for eight weeks. The cecal DNA samples were subjected to 16s rRNA sequencing (by Novogene, Inc.). The heatmap of the abundance changes is shown at the phylum level only. (A color version of this figure is available in the online journal.)

Figure 2.

Regulation of microbiota homeostasis by immunoglobulin A (IgA) and carotenoids. Commensal microbiota can induce Treg cells via Myd88 signaling to up-regulate the T Follicular Helper cells, which in turn stimulates the plasma cells to produce IgA. The increased opportunistic bacterial pathogens (OBP) inhibit the commensal microbiota, leading to suppression of IgA production in the plasma cells. OBP also triggers the enhanced expression of macrophage inflammatory protein 2 (MIP-2), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), inflammation-associated factors in the gut tissue. Dietary carotenoids (including pro-vitamin A carotenoids and non-pro-vitamin A carotenoids, e.g. xanthophylls) and their supplementation may increase the production of retinoic acid (RA). RA sequentially induces the maturation of gut immune system, e.g. B cell activation, and IgA production. Xanthophylls activate T cells and natural killer cells resulting in the production of IFN-γ. IFN-γ further stimulates the differentiation and maturation of B cells to produce IgA, and in turn promote the gut health. (A color version of this figure is available in the online journal.)