Lack of Vitamin D Receptor Causes Dysbiosis and Changes the Functions of the Murine Intestinal Microbiome

Jin, D. P.; Wu, Shaoping; Zhang, Yong Guo; Lü, Rong; Xia, Yinglin; Dong, Hui; Sun, Jun

doi:10.1016/j.clinthera.2015.04.004

Cited by 204 publications

(156 citation statements)

References 51 publications

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“…45 Recently, Clostridium , a member of Clostridia class, was shown to be more abundant in VDR−/− mice compared with WT, suggesting an inhibitory effect of vitamin D on the abundance Clostridium. 53 This is consistent with our findings of lower abundance of members of Clostridia class in high quartile vs low quartile of serum vitamin D.…”

Section: Discussionsupporting

confidence: 92%

Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans

Ciubotaru

Green

Kukreja

et al. 2015

Translational Research

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The importance of gut microbiota in pathogenesis of diabetes remains unknown. This study investigated the relationship between microbiota and metabolic markers in African American men (AAM) with prediabetes and hypovitaminosis D. The study was ancillary to a randomized trial of vitamin D supplementation with weekly ergocalciferol (50,000 IU) conducted in AAM veterans over 12 months (D Intervention in Veterans Affairs). Glycemic groups (Gr) were characterized based on changes in oral glucose tolerance between baseline and exit. Subjects with stable normal glucose tolerance were assigned to Gr-1 and those with stable prediabetes (impaired glucose tolerance and impaired fasting glucose) to Gr-2. Microbiota composition was analyzed in stool collected at the exit (n = 115) and compared between Gr-1 and Gr-2, as well as between the lowest and highest quartiles of dietary intake of energy and fat, hemoglobin A1c, and serum 25-hydroxyvitamin D (25[OH]D) level. Differences between Gr-1 and Gr-2 included the Bacteroidetes/Firmicutes and Bacteroidales/Clostridia ratios and differences in genera such as Ruminococcus and Dialister. Changes in specific taxa associated with the lowest and highest quartiles of 25(OH) D (eg, Ruminococcus, Roseburia, Blautia, Dorea) were clearly distinct from those of dietary intake (eg, Bacteroides, Bacteroides/Prevotella ratio) or A1c (eg, Faecalibacterium, Catenibacterium, Streptococcus). These findings suggest a novel interaction between microbiota and vitamin D and a role for microbiota in early stages of diabetes development. Although results suggest that specific taxa are associated with glycemic stability over time, a causative relationship between microbiota makeup and dysglycemia is still to be demonstrated.

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Section: Discussionsupporting

confidence: 92%

Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans

Ciubotaru

Green

Kukreja

et al. 2015

Translational Research

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“…Vitamin D is also believed to be a factor in regulating gut bacterial homeostasis. Studies in mice of both Vitamin D and Vitamin D receptor (VDR) deficiency have shown composition changes in the intestinal microbiota, with a decrease in Lactobacilli and Firmicutes and an increase in Clostridium and Bacteroidetes in the fecal stool when compared to WT mice [51–54]. Lactobacilli are Gram-positive, fermentative bacteria that produce lactic acid, which has anti-inflammatory and anti-tumorigenic effects by balancing intestinal homeostasis [51].…”

Section: Diet and The Microbiomementioning

confidence: 99%

“…Studies in mice of both Vitamin D and Vitamin D receptor (VDR) deficiency have shown composition changes in the intestinal microbiota, with a decrease in Lactobacilli and Firmicutes and an increase in Clostridium and Bacteroidetes in the fecal stool when compared to WT mice [51–54]. Lactobacilli are Gram-positive, fermentative bacteria that produce lactic acid, which has anti-inflammatory and anti-tumorigenic effects by balancing intestinal homeostasis [51]. Vitamin D deficiency, with a decrease in lactic acid producing bacteria and an increase in potentially pathogenic bacteria, may increase the risk of chronic inflammation and the following colitis-associated CRC development.…”

Section: Diet and The Microbiomementioning

confidence: 99%

Current Understanding of Dysbiosis in Disease in Human and Animal Models

DeGruttola

Low

Mizoguchi

et al. 2016

Inflammatory Bowel Diseases

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Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects over two million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed “dysbiosis”. In spite of the extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, we have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments in order to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases.

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“…33 The secondary bile acid lithocholic acid, which is produced by Clostridium bacteria in the gut lumen, inhibits the Th1 immune response and suppresses IFNγ and IL-2 production by activating VDR in T cells. 66 Vdr knockout mice have lower Clostridium in the gut, 60 illustrating the influence of crosstalk between the microbiome and VDR signaling in immunity. Butyrate, a short chain fatty acid produced by gut microbes, can increase epithelial VDR expression and thus decrease production of pro-inflammatory cytokines.…”

Section: Vdr Signaling Regulates the Gut Microbiotamentioning

confidence: 99%

Ancient Nuclear Receptor VDR With New Functions: Microbiome and Inflammation

Bakke

Sun

2018

Inflammatory Bowel Diseases

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108

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Nuclear receptor vitamin D receptor (VDR) regulates most of the biological actions of the active vitamin D metabolite, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). VDR is highly expressed in intestine and is a critical regulator of proliferation and differentiation, intestinal barrier function, innate immunity, and host defense in the gut. Evidence strongly supports a protective effect of vitamin D and VDR in inflammatory bowel diseases (IBD). Emerging evidence demonstrates low VDR expression and dysfunction of vitamin D/VDR signaling in patients with IBD. In the current review, we summarize recent progress made in vitamin D/VDR signaling in genetic regulation, immunity, and microbiome in both ulcerative colitis and Crohn’s disease. We cover the mechanisms of intestinal VDR in regulating inflammation through inhibiting the NF-κB pathway and activating autophagy. Recent studies suggest that the association of VDR SNPs with immune and intestinal pathology may be gender-dependent. We emphasize the tissue specificity of VDR and its gender and time-dependent effects. Furthermore, we discuss potential clinical application and future direction of vitamin D/VDR in prevention and treatment of IBD.

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Lack of Vitamin D Receptor Causes Dysbiosis and Changes the Functions of the Murine Intestinal Microbiome

Cited by 204 publications

References 51 publications

Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans

Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans

Current Understanding of Dysbiosis in Disease in Human and Animal Models

Ancient Nuclear Receptor VDR With New Functions: Microbiome and Inflammation

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