Mucosal vitamin D signaling in inflammatory bowel disease

• Published in: Autoimmunity reviews Vol. 19; no. 11; p. 102672
• Main Authors: Kellermann, Lauge, Jensen, Kim Bak, Bergenheim, Fredrik, Gubatan, John, Chou, Naomi D., Moss, Alan, Nielsen, Ole Haagen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2020
• Subjects: Cell signaling; Gastrointestinal Microbiome; Humans; Inflammatory bowel disease; Inflammatory Bowel Diseases; Intestinal barrier; Intestinal Mucosa - immunology; Signal Transduction; Tight Junctions; Vitamin D; Vitamin D - physiology; Vitamin D receptor; Inflammatory bowel disease; Intestinal barrier; Vitamin D; Vitamin D receptor; Cell signaling
• ISSN: 1568-9972; 1568-9972; 1873-0183
• DOI: 10.1016/j.autrev.2020.102672

Epidemiological studies have identified vitamin D (25(OH)D) deficiency to be highly prevalent among patients with inflammatory bowel disease (IBD), and low serum levels correlate with a higher disease activity and a more complicated disease course. The link to IBD pathogenesis has been subject of investigations, primarily due to the distinct immunological functions of vitamin D signaling, including anti-inflammatory and anti-fibrotic actions. Vitamin D is a pleiotropic hormone that executes its actions on cells through the vitamin D receptor (VDR). A leaky gut, i.e. an insufficient intestinal epithelial barrier, is thought to be central for the pathogenesis of IBD, and emerging data support the concept that vitamin D/VDR signaling in intestinal epithelial cells (IECs) has an important role in controlling barrier integrity. Here we review the latest evidence on how vitamin D promotes the interplay between IECs, the gut microbiome, and immune cells and thereby regulate the intestinal immune response. On the cellular level, vitamin D signaling regulates tight junctional complexes, apoptosis, and autophagy, leading to increased epithelial barrier integrity, and promotes expression of antimicrobial peptides as part of its immunomodulating functions. Further, intestinal VDR expression is inversely correlated with the severity of inflammation in patients with IBD, which might compromise the positive effects of vitamin D signaling in patients with flaring disease. Efforts to reveal the role of vitamin D in the pathophysiology of IBD will pave the road for the invention of more rational treatment strategies of this debilitating disease in the future. •Low levels of serum vitamin D are associated with adverse clinical outcomes in IBD.•Vitamin D signaling modulates the intestinal microbiome and immune functions.•Intestinal barrier integrity is maintained by vitamin D.•Vitamin D signaling alters the expression of known IBD risk genes.