Vitamin D Signaling in Gastro-Rheumatology: From Immuno-Modulation to Potential Clinical Applications

Pagnini, Cristiano; Picchianti-Diamanti, Andrea; Bruzzese, Vincenzo; Lorenzetti, Roberto; Luchetti, Michele Maria; Martin, Luis Severino Martin; Pica, Roberta; Scolieri, Palma; Scribano, Maria Lia; Zampaletta, Costantino; Chimenti, Maria Sole; Laganà, Bruno

doi:10.3390/ijms22052456

Cited by 5 publications

(5 citation statements)

References 118 publications

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“…Vitamin D increases the expression of TJ proteins such as claudin and occludin [ 215 ]. It also regulates antimicrobial responses on the intestinal surface and improves gut dysbiosis [ 216 ]. In particular, vitamin D supplementation increases the microbiota diversity of the gut microbiota and decreases the Firmicutes/Bacteroidetes ratio [ 217 ].…”

Section: Therapeutic Interventions To Restore Intestinal Barrier Integritymentioning

confidence: 99%

Intestinal Barrier in Human Health and Disease

Tommaso

Gasbarrini

Ponziani

2021

IJERPH

244

110

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The intestinal mucosa provides a selective permeable barrier for nutrient absorption and protection from external factors. It consists of epithelial cells, immune cells and their secretions. The gut microbiota participates in regulating the integrity and function of the intestinal barrier in a homeostatic balance. Pathogens, xenobiotics and food can disrupt the intestinal barrier, promoting systemic inflammation and tissue damage. Genetic and immune factors predispose individuals to gut barrier dysfunction, and changes in the composition and function of the gut microbiota are central to this process. The progressive identification of these changes has led to the development of the concept of ‘leaky gut syndrome’ and ‘gut dysbiosis’, which underlie the relationship between intestinal barrier impairment, metabolic diseases and autoimmunity. Understanding the mechanisms underlying this process is an intriguing subject of research for the diagnosis and treatment of various intestinal and extraintestinal diseases.

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Section: Therapeutic Interventions To Restore Intestinal Barrier Integritymentioning

confidence: 99%

Intestinal Barrier in Human Health and Disease

Tommaso

Gasbarrini

Ponziani

2021

IJERPH

244

110

View full text Add to dashboard Cite

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“…Vitamin D affects both T cell activation and differentiation (17)(18)(19). Vitamin D reduces IFNg and IL-17 and increases IL-4 and IL-13 secretion (10,17,(20)(21)(22), hence vitamin D is thought to skew immune responses away from T helper (Th) 1/Th17 towards Th2 dominated responses. Importantly, vitamin D exerts its function via the vitamin D receptor (VDR) that is expressed by various immune cells (18).…”

Section: Introductionmentioning

confidence: 99%

Normal T and B Cell Responses Against SARS-CoV-2 in a Family With a Non-Functional Vitamin D Receptor: A Case Report

et al. 2021

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The coronavirus disease 2019 (COVID-19) pandemic has severely impacted daily life all over the world. Any measures to slow down the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to decrease disease severity are highly requested. Recent studies have reported inverse correlations between plasma levels of vitamin D and susceptibility to SARS-CoV-2 infection and COVID-19 severity. Therefore, it has been proposed to supplement the general population with vitamin D to reduce the impact of COVID-19. However, by studying the course of COVID-19 and the immune response against SARS-CoV-2 in a family with a mutated, non-functional vitamin D receptor, we here demonstrate that vitamin D signaling was dispensable for mounting an efficient adaptive immune response against SARS-CoV-2 in this family. Although these observations might not directly be transferred to the general population, they question a central role of vitamin D in the generation of adaptive immunity against SARS-CoV-2.

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“…VDR is a single aminoacidic chain polypeptide of the nuclear receptors superfamily, and it is widely and differently expressed in many tissues, including intestinal mucosa and immune cells ( Pike et al, 2017 ). The binding of 1,25(OH)2D to VDR in the cytoplasm of the cell, with the heterodimerization with the retinoid X receptor (RXR), determines the translocation of the complex to the nucleus and the binding to vitamin D response elements (VDREs), with stimulation and/or suppression of gene transcription ( Pagnini et al, 2021 ). The biologic action of vitamin D/VDR signalling, initially characterized in the bone metabolism, is pleiotropic, and the correct functioning of this pathways has a paramount role for homeostasis maintenance at several levels.…”

Section: Probiotics In Ibd: Potential Mechanism Of Action and Clinical Evidencementioning

confidence: 99%

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

et al. 2021

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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.

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Vitamin D Signaling in Gastro-Rheumatology: From Immuno-Modulation to Potential Clinical Applications

Cited by 5 publications

References 118 publications

Intestinal Barrier in Human Health and Disease

Intestinal Barrier in Human Health and Disease

Normal T and B Cell Responses Against SARS-CoV-2 in a Family With a Non-Functional Vitamin D Receptor: A Case Report

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

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