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.
Highlights
In the last decades, virtually every field of human science has been involved and shaked by the effect of the so called “microbiome revolution.” under the stimulation of novel cultureindependent laboratory techniques, that allowed a thorough evaluation of bacterial intestinal species, and thank to an increased comprehension of the molecular mediators of microbiota-intestine interaction, an exponential and intensive interest rising has led to a consistent impulse to this field of research (Rescigno, 2017)
Besides the aforementioned beneficial effect that probiotics and vitamin D may singularly exert in Inflammatory bowel diseases (IBD) patients, early experimental data are suggesting a possible direct interaction between those two nutraceuticals, that may confer increased anti-inflammatory effect in the intestinal mucosa
Wu et al demonstrated that Lactobacillus rhamnosus GG and Lactobacillus plantarum stimulated vitamin D receptor (VDR) expression and activity in different cell lines, and that the administration of the two probiotic bacteria had a protective effect against Salmonella-induced colitis only in wild-type mice with intact functioning of the VDR pathway, while that protective effect was completely abrogated in VDR knock-out (KO) mice (Wu et al, 2015a)
Summary
Virtually every field of human science has been involved and shaked by the effect of the so called “microbiome revolution.” under the stimulation of novel cultureindependent laboratory techniques, that allowed a thorough evaluation of bacterial intestinal species, and thank to an increased comprehension of the molecular mediators of microbiota-intestine interaction, an exponential and intensive interest rising has led to a consistent impulse to this field of research (Rescigno, 2017). By means of an accurate microbiota composition analysis, difference between health subjects and patients with different diseases has been characterized, with the final ideal goal to identify bacterial species of particular relevance for the pathologic condition, potentially useful as novel probiotic bacteria (“ generation probiotics”) to supplement for therapeutic purposes (O’Toole et al, 2017). A consistent set of experimental and pre-clinical data indicate potential mechanisms of action by which specific probiotic bacteria may exert a beneficial effect on chronic intestinal inflammation (Ciorba, 2012). Probiotics may contrast the dysbiosis by reducing pathogenic bacteria and stimulating beneficial ones, such as butirrateproducing bacteria (Markowiak-Kopec and Slizewska, 2020) They may temporary colonize the intestinal mucosa and directly interact with specific receptors of the innate immune system, namely the pattern recognition receptors - PRR (i.e., nucleotide-binding oligomerization domain - NOD and tolllike receptors - TLRs), exerting an immunomodulatory effect (Bermudez-Brito et al, 2012). Since the correction in deficient IBD patients appears rational and indicated, the beneficial effect of vitamin D supplement in patients with normal serum level is not straightforward and probably needs further investigation
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