Relationships Between Vitamin D, Gut Microbiome, and Systemic Autoimmunity

Abstract

There is increasing recognition of the role the microbiome plays in states of health and disease. Microbiome studies in systemic autoimmune diseases demonstrate unique microbial patterns in Inflammatory Bowel Disease, Rheumatoid Arthritis, and Systemic Lupus Erythematosus to a lesser extent, whereas there is no single bug or pattern that characterizes Multiple Sclerosis. Autoimmune diseases tend to share a predisposition for vitamin D deficiency, which alters the microbiome and integrity of the gut epithelial barrier. In this review, we summarize the influence of intestinal bacteria on the immune system, explore the microbial patterns that have emerged from studies on autoimmune diseases, and discuss how vitamin D deficiency may contribute to autoimmunity via its effects on the intestinal barrier function, microbiome composition, and/or direct effects on immune responses.

Keywords: autoimmune disease; bacterial composition; gut barrier; microbiome; vitamin D.

Figure 1

Schematic of the physical and functional intestinal epithelial barrier. The physical barrier is composed of a thin and thick mucus layer, followed by single cell layer consisting of enterocytes, Paneth cells, goblet cells, and microfold (M) cells. The integrity of this layer is maintained via intact tight junctions. Functionally, the epithelium produces mucin and antimicrobial peptides, and allows translocation of secretory immunoglobulin A. Intestinal immune cells sample the luminal environment, respond to invasive pathogens, and coordinate innate and adaptive immune responses. SCFA, vitamin D, and polysaccharide A have all been shown to promote regulatory adaptive responses, whereas bacteria generally promote proinflammatory responses. SCFA, short chain fatty acids; PsA, polysaccharide A; sIgA, secretory IgA; Ag, antigen; M cell, microfold cell. Illustration by David Schumick, BS, CMI. Reprinted with the permission of the Cleveland Clinic Center for Medical Art & Photography © 2019. All rights reserved.

Figure 2

Model of the interactions between genetics, gut integrity, microbiome, and vitamin D deficiency. Genetic predisposition can influence vitamin D activity, integrity of the gut barrier, and basal level of immune activation. Low vitamin D increases the permeability of the gut barrier and heightens immune activity. Furthermore, low vitamin D and permeability of the gut alter microbial composition and the ability of microbes to translocate across the intestinal epithelium, leading to interaction with the host immune system. Ultimately, immune system activation contributes to autoimmunity. Δ = change. Illustration by David Schumick, BS, CMI. Reprinted with the permission of the Cleveland Clinic Center for Medical Art & Photography © 2019. All rights reserved.