“…Notably, there is a growing body of evidence suggesting that VDR activation has a regulatory role in mutualistic intestinal virome-host interactions, and more information on the interactions between the sensing of vitamin D and VDR is needed. 89 Figure 8. The interrelations of the host, bacteria, and virus.…”
Vitamin D receptor (VDR) deficiency is associated with cancer, infection, and chronic inflammation. Prior research has demonstrated VDR regulation of bacteria; however, little is known regarding VDR and viruses. We hypothesize that VDR deficiency impacts on the intestinal virome and viral-bacterial interactions. We specifically deleted VDR from intestinal epithelial cells (VDR
ΔIEC
), Paneth cells (VDR
ΔPC
), and myeloid cells (VDR
ΔLyz
) in mice. Feces were collected for shotgun metagenomic sequencing and metabolite profiling. To test the functional changes, we evaluated pattern recognition receptors (PRRs) and analyzed microbial metabolites.
Vibrio
phages,
Lactobacillus
phages, and
Escherichia coli
typing phages were significantly enriched in all three conditional VDR-knockout mice. In the VDR
ΔLyz
mice, the levels of eight more virus species (2 enriched, 6 depleted) were significantly changed. Altered virus species were primarily observed in female VDR
ΔLyz
(2 enriched, 3 depleted) versus male VDR
ΔLyz
(1 enriched, 1 depleted). Altered alpha and beta diversity (family to species) were found in VDR
ΔLyz
. In VDR
ΔIEC
mice, bovine viral diarrhea virus 1 was significantly enriched. A significant correlation between viral and bacterial alterations was found in conditional VDR knockout mice. There was a positive correlation between
Vibrio
phage JSF5 and
Cutibacterium acnes
in VDR
ΔPC
and VDR
ΔLyz
mice. Also, there were more altered viral species in female conditional VDR knockout mice. Notably, there were significant changes in PRRs: upregulated TLR3, TLR7, and NOD2 in VDR
ΔLyz
mice and increased CLEC4L expression in VDR
ΔIEC
and VDR
ΔPC
mice. Furthermore, we identified metabolites related to virus infection: decreased glucose in VDR
ΔIEC
mice, increased ribulose/xylulose and xylose in VDR
ΔLyz
mice, and increased long-chain fatty acids in VDR
ΔIEC
and VDR
ΔLyz
female mice. Tissue-specific deletion of VDR changes the virome and functionally changes viral receptors, which leads to dysbiosis, metabolic dysfunction, and infection risk. This study helps to elucidate VDR regulating the virome in a tissue-specific and sex-specific manner.
“…Notably, there is a growing body of evidence suggesting that VDR activation has a regulatory role in mutualistic intestinal virome-host interactions, and more information on the interactions between the sensing of vitamin D and VDR is needed. 89 Figure 8. The interrelations of the host, bacteria, and virus.…”
Vitamin D receptor (VDR) deficiency is associated with cancer, infection, and chronic inflammation. Prior research has demonstrated VDR regulation of bacteria; however, little is known regarding VDR and viruses. We hypothesize that VDR deficiency impacts on the intestinal virome and viral-bacterial interactions. We specifically deleted VDR from intestinal epithelial cells (VDR
ΔIEC
), Paneth cells (VDR
ΔPC
), and myeloid cells (VDR
ΔLyz
) in mice. Feces were collected for shotgun metagenomic sequencing and metabolite profiling. To test the functional changes, we evaluated pattern recognition receptors (PRRs) and analyzed microbial metabolites.
Vibrio
phages,
Lactobacillus
phages, and
Escherichia coli
typing phages were significantly enriched in all three conditional VDR-knockout mice. In the VDR
ΔLyz
mice, the levels of eight more virus species (2 enriched, 6 depleted) were significantly changed. Altered virus species were primarily observed in female VDR
ΔLyz
(2 enriched, 3 depleted) versus male VDR
ΔLyz
(1 enriched, 1 depleted). Altered alpha and beta diversity (family to species) were found in VDR
ΔLyz
. In VDR
ΔIEC
mice, bovine viral diarrhea virus 1 was significantly enriched. A significant correlation between viral and bacterial alterations was found in conditional VDR knockout mice. There was a positive correlation between
Vibrio
phage JSF5 and
Cutibacterium acnes
in VDR
ΔPC
and VDR
ΔLyz
mice. Also, there were more altered viral species in female conditional VDR knockout mice. Notably, there were significant changes in PRRs: upregulated TLR3, TLR7, and NOD2 in VDR
ΔLyz
mice and increased CLEC4L expression in VDR
ΔIEC
and VDR
ΔPC
mice. Furthermore, we identified metabolites related to virus infection: decreased glucose in VDR
ΔIEC
mice, increased ribulose/xylulose and xylose in VDR
ΔLyz
mice, and increased long-chain fatty acids in VDR
ΔIEC
and VDR
ΔLyz
female mice. Tissue-specific deletion of VDR changes the virome and functionally changes viral receptors, which leads to dysbiosis, metabolic dysfunction, and infection risk. This study helps to elucidate VDR regulating the virome in a tissue-specific and sex-specific manner.
“…The physiological relevance of these changes will be assessed in the future in digestive disease and infectious models. Notably, there is a growing body of evidence suggesting that VDR activation has a regulatory role in mutualistic intestinal virome-host interactions, and more information on the interactions between the sensing of vitamin D and VDR is needed [84]. comparisons are shown with fold-changes (logFCs) and q-values in three comparisons between the conditional VDR knockout groups (VDRΔIEC, VDRΔPC, and VDRΔLyz) and control mice (VDRLoxP).…”
Background Vitamin D receptor (VDR) is highly conserved in mammals, and its deficiency is associated with various diseases (e.g., cancer, infection, and chronic inflammation). Prior research has described the effect of VDR on bacteria; however, little is known regarding the effects of VDR on viruses. We hypothesize that VDR is a regulator of the virome and virus-bacterial interactions. We conditionally deleted VDR from intestinal epithelial cells (VDRΔIEC), Paneth cells (VDRΔPC), and myeloid cells (VDRΔLyz) in mice. Feces were collected for shotgun metagenomic sequencing and metabolite profiling. To test the functional changes, we evaluated pattern recognition receptors (PRRs) and analyzed microbial metabolites. Results Vibrio phages, Lactobacillus phages and Escherichia coli typing phages were significantly enriched in all three conditional VDR-knockout mice compared to VDRLoxP mice. In the VDRΔLyz mice, the levels of eight more virus species (2 enriched, 6 depleted) were significantly changed. These significantly altered virus species were primarily observed in female VDRΔLyz (2 enriched, 3 depleted) versus male VDRΔLyz (1 enriched, 1 depleted). Altered alpha and beta diversity were found in VDRΔLyz (family to species). In VDRΔIEC mice, bovine viral diarrhea virus 1 was significantly enriched. Overall, these significantly altered virus species were more often observed in female VDRΔIEC mice (2 enriched, 5 depleted) versus male mice (none). A significant correlation between viral and bacterial alterations was found in conditional VDR knockout mice. There was a positive correlation between Vibrio phage JSF5 and Cutibacterium acnes in VDRΔPC and VDRΔLyz mice. Also, there were more altered viral species in female conditional VDR knockout mice. Notably, there were significant changes in PRRs: upregulated TLR3, TLR7, and NOD2 in VDRΔLyz mice and increased CLEC4L expression in VDRΔIEC and VDRΔPC mice. Furthermore, we identified metabolites related to virus infection: decreased glucose in VDRΔIEC mice, increased ribulose/xylulose and xylose in VDRΔLyz mice, and increased long-chain fatty acids in VDRΔIEC and VDRΔLyz female mice. Conclusion Tissue-specific deletion of VDR changes the virome and functionally changes viral receptors, which leads to dysbiosis, metabolic dysfunction, and infection risk. This study helps to elucidate VDR regulation of the virome in a tissue-specific and sex-specific manner.
“…Vitamin D has been shown to play a role in the defense against bacteria by inducing the production of cathelicidin, an antimicrobial peptide, in macrophages, but also in the intestinal epithelium. It has been suggested that this may affect the interplay between the microbiota and the epithelium in IBD, as well as the previously established effect against mycobacterial infection (27,74,75).…”
Section: Vitamin D and Autoimmunitymentioning
confidence: 95%
“…Vitamin D deficiency has been shown to increase the risk for colitis in animal models (48,85). More recent studies support that vitamin D may affect mucosal immunity by modulating the interaction between microbiota and the intestinal epithelium (74,75). In several clinical observational and cross-sectional studies, vitamin D deficiency has been associated with increased IBD disease activity (71,85).…”
Vitamin D deficiency was common, especially in CD, and was associated with increased disease activity, a relapsing disease course and higher inflammatory activity.
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