Probiotics and Vitamin D/Vitamin D Receptor Pathway Interaction: Potential Therapeutic Implications in Inflammatory Bowel Disease

Abstract

Inflammatory bowel diseases (IBD) are chronic conditions of unknown etiology and immunomediated pathogenesis. In the last years, the comprehension of the complex mechanisms involved in the intestinal mucosal homeostasis, and the analysis of the alterations potentially leading to inflammatory pathologic states, has consistently increased. Specifically, the extraordinary impulse in the field of research of the intestinal microbiome has opened the door to the investigation of possible novel approaches to the diagnosis, management and therapeutic applications in IBD. In line with that, administration of probiotic bacteria has been intensely evaluated, leading to much more exciting results in experimental models than in clinical practice. Considering the consistent heterogeneity of the available studies on probiotics, the increased knowledge of the properties of the single bacterial species would ideally lead to unravel potential mechanisms of action that may bring therapeutic applications in specific pathologic condition. Among the relevant molecular pathways for mucosal homeostasis maintenance, the vitamin D/vitamin D receptor (VDR) pathway has been intensely studied in the very last years. In fact, besides osteometabolic functions, the vitamin D exerts important homeostatic effects in the organism at multiple levels, such as immunomodulation, inflammation control, and microbiota regulation, which are likely to play a relevant role in intestinal mucosa protection. In the present review, recent findings about probiotic applications in IBD and mechanisms of action linking vitamin D/VDR pathway to IBD are reported. Available evidence for probiotic effect on vitamin D/VDR are reviewed and potential future application in IBD patients are discussed. At present, many aspects of IBD pathogenesis are still obscure, and current therapeutic options for IBD treatment are at best suboptimal. The increasing comprehension of the different pathways involved in IBD pathogenesis will lead to novel findings ideally leading to potential clinical applications. Microbiota manipulation and vitamin/VDR pathway appear a promising field for future research and therapeutic developments.

Advances in the Study of Probiotics for Immunomodulation and Intervention in Food Allergy

“…As research progresses, it is increasingly evident that probiotic components could enhance intestinal epithelial barrier function [ 67 ]. Probiotics regulate intestinal epithelial homeostasis by promoting intestinal epithelial cell survival, enhancing barrier function, and stimulating protective responses while at the same time regulating host cell signaling pathways, including protein kinase B (Akt) signaling pathway, mitogen-activated protein kinase, and nuclear factor-κB [ 68 ]. Similarly, Rajput et al found that probiotics stimulate epithelial cells and activate dendritic cells through toll-like receptors, producing cytokines [ 69 ].…”

Vitamin D and malabsorptive gastrointestinal conditions: A bidirectional relationship?

“…Further experimental data demonstrated that probiotics stimulate VDR expression and activity. Besides the effect on VDR, some clinical and experimental data indicate that probiotic bacteria may increase vitamin D levels [ 34 ]. In the gut lumen, the mucus layer and the underlying epithelium serve to keep resident microbiota at bay [ 35 , 36 ].…”

“…A meta-analysis evaluating 16 studies including 1338 patients with IBDs and 808 controls has been published [78]. The mean ages (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) and gender distribution (49-53% women) were similar between the two groups. Along with a significantly lower mean BMD and Z-scores for IBD patients versus controls at all sites (femoral neck, total femur and lumbar spine), there was a significant 38% increase in global risk of fractures.…”

Vitamin D as a Nutri-Epigenetic Factor in Autoimmunity—A Review of Current Research and Reports on Vitamin D Deficiency in Autoimmune Diseases

“…The interplay of bacterial metabolites, butyrate, and lithocholic acid, as well as bacterial enzymes (e.g., capable of activating vitamin D) and growth factors on VDR signaling and the course of inflammation, has also been explored [ 75 ]. Guidelines on the practical use of probiotics as valuable components of treatment in IBD are also expected in the future [ 79 ].…”