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©The Author(s) 2016.
World J Gastroenterol. Jan 21, 2016; 22(3): 933-948
Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.933
Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.933
Strain | Model | Vitamin D metabolite/analog | Dose, route | Treatment window and duration | Serum vit D measure | Outcome | Ref. |
Vitamin D Supplementation | |||||||
Protection | |||||||
Il10-/- | Spontaneous | 1,25(OH)2D3 and D3 | 0.005 μg 1,25(OH)2D3/d or 5 μg D3/d, diet | 3 wk of age; maintained throughout study | ND | Ameliorated IBD | [40] |
0.2 μg 1,25(OH)2D3/d, diet | At the first sign of IBD (diarrhea), lasted for 2 wk | Effective at blocking the progression and ameliorating the symptoms in established disease | |||||
Il10-/- | Spontaneous | 1,25(OH)2D3 | 20 ng/d, diet | 4 wk of age; maintained throughout study | ND | Significantly reduced spontaneous colitis. More effective protection with combined treatment with calcium | [113] |
C57BL/6 | DSS (0.5-3.5%), 5 d | 1,25(OH)2D3 | 50 ng/d, diet or 10 ng, intrarectally | Diet given 1 wk prior to DSS treatment; maintained throughout study. Intrarectal administration given 1 d prior to DSS; given every other day | ND | Decreased DSS-induced colitis. Intrarectal administration more effective than dietary delivery | [106] |
Balb/c | DSS (3%), 7 d | ZK191784 (1,25(OH)2D3 analog) | 100 μg/kg per day, orally | 3 d prior or at the start of DSS treatment; given daily | ND | Significantly decreased DSS-induced colitis | [115] |
C57BL/6 | DSS (3%), 7 d | 1,25(OH)2D3 | 0.5 μg/kg, IP | 1 d prior to DSS treatment; given daily up to 11 d | ND | Decreased inflammation and tissue damage following DSS treatment; Increased weight loss likely due to hypercalcemia | [41] |
C57BL/6 | DSS (2%), 7 d | 1,25(OH)2D3 | 0.2 μg/25 g BW/d, oral gavage | After DSS treatment | ND | Decreased clinical disease, colonic inflammation and intestinal permeability following DSS treatment | [117] |
Cyp27b1-/- and Vdr-/- | DSS (3.5%), 5 d | 1,25(OH)2D3 | 50 ng/d, diet | 2 wk prior to DSS treatment; maintained throughout study | ND | Cyp27b1-/- mice more susceptible to DSS-induced colitis; supplementation with 1,25(OH)2D3 partially ameliorated disease | [91] |
C57BL/6 | DSS (3%), 7 d | NA | Adoptive transfer of CYP27B1 over-expressing monocytes | Adoptive transfer on 5th day of DSS treatment | ND | CD11b+/Gr1+ monocytes overexpressing CYP27B1 trafficked to the inflamed colon and ameliorated DSS-induced colitis | [114] |
C57BL/6 | DSS (2%), 5 d of treatment followed by 2 d of regular water throughout study | 1,25(OH)2D3 | 0.2 μg/25 g BW/d, oral gavage | 2 wk after initiation of DSS treatment; maintained throughout study | ND | Vitamin D decreased clinical disease and colonic inflammation following DSS treatment. Vitamin D treatment significantly decreased mononuclear cell infiltrates present in the spleen and mesenteric lymph node following DSS | [139] |
Smad3-/- | Helicobacter bilis | D3 | 1000 IU or 5000 IU per kg diet, diet | 2 wk prior to H. bilis infection; maintained throughout study | 25(OH)D | Higher vitamin D significantly decrease colonic inflammation | [39] |
Balb/c | TNBS (100 mg/kg) | 1,25(OH)2D3 | 0.2 μg/kg, IP | Given 2 h before and 3 d post (acute) or 3, 4 and 5 d post TNBS (interventional) | ND | Significantly reduced colitis; greater protection with concurrent treatment with dexamethasone | [140] |
C57BL/6 | TNBS (100 mg/kg) | Paracalitriol (1,25(OH)2D3 analog) | 0.5 μg/kg, IP | Given 30 min before and 1, 3 and 5 d post TNBS | ND | Ameliorated TNBS colitis and protected against epithelial barrier disruption | [116] |
Neutral | |||||||
Il10-/- | Spontaneous colitis | D3 | 25 IU or 5000 IU per kg diet, diet | Before conception; maintained throughout study | 25(OH)D | No significant difference in inflammation score | [109] |
Rag-/- | Adoptive transfer of Il10-/- T cells + piroxicam (7 d) | D3 | 1000 IU or 5000 IU per kg diet, diet | After peroxicam treatment ends; for 12 d | 1,25(OH)2D, 25(OH)D | Vitamin D supplementation during active colitis did not alter colonic inflammation; increased trabecular bone deterioration | [108] |
Exacerbation | |||||||
C57BL/6 | Citrobacter rodentium | 1,25(OH)2D3 | 0.5 μg/kg, IP | 1 d prior to treatment; daily | ND | Increased colonic ulceration and bacterial burdens compared to controls | [41] |
Vitamin D Deficiency | |||||||
Il10-/- | Spontaneous | NA | Vit D deficient diet | Maintain throughout study | ND | Increased mortality and more rapid disease development compared to vitamin D sufficient animals | [40] |
C57BL/6 | DSS (2.5%), 6 d | NA | Vit D deficient diet | 6 wk prior to DSS treatment; maintained throughout study | 25(OH)D | Exacerbated DSS colitis and increased bacterial loads within the colonic tissue | [105] |
Il10-/- | AOM + DSS (2%), 7 d | NA | Vit D deficient diet | 3 wk of age; maintained throughout study | 25(OH)D | Increased mortality and disease severity in AOM/DSS colitis | [141] |
Smad3-/- | Helicobacter bilis | NA | Vit D deficient diet | 2 wk prior to infection; maintain throughout study | 25(OH)D | Did not alter IBD development or severity | [39] |
Il10-/- | DSS (2%), 9 days or E. coli | NA | Vit D deficient diet | Maintain throughout experiment | 1,25OH)2D and 25(OH)D | Decreased survival and increased intestinal permeability following DSS treatment; increased susceptibility to infection with invasive E. coli | [103] |
Other (genetically altered VDR) | |||||||
hVDR Tg | TNBS, DSS, and adoptive T cell transfer | NA | NA | NA | ND | Overexpression of VDR in the intestinal epithelial cells protected against TNBS, DSS and adoptive T cell transfer -induced colitis | [77] |
hVDR Tg Il10-/- | Spontaneous | NA | NA | NA | ND | Overexpression of VDR in the intestinal epithelial cells protected against spontaneous disease in Il10-/- mice | [142] |
Vdr-/- | DSS (0.5%-3.5%), 5 d | NA | NA | NA | ND | Increased sensitivity, mortality and disease severity in response to DSS | [107] |
Vdr-/- | DSS (2%-2.5%), 7 d | NA | NA | NA | ND | More sensitive to DSS inducted colitis resulting in severe mucosal ulcerations, impaired mucosal wound healing, decreased epithelial barrier function and increased mortality | [102] |
Vdr-/- | Salmonella typhimurium | NA | NA | NA | ND | Administration of probiotics (Lactobacillus rhamnosus and Lactobacillus plantarum) increased VDR protein expression in colon epithelial cells. Probiotic administration protected against Salmonella-induced colitis in wild type but not Vdr-/- mice | [138] |
VDRΔIEC | DSS (5%), 7 d | NA | NA | NA | ND | Loss of intestinal epithelial VDR exacerbated DSS colitis, altered paneth cell development and changed autophagy gene expression | [137] |
Vdr-/- and Il10-/-/Vdr-/- | Adoptive T Cell Transfer and Spontaneous | NA | NA | NA | ND | Il10-/-/Vdr-/- mice developed more severe IBD and increased mortality compared to Il10-/- mice. Adoptive transfer of Vdr-/- CD4 T cells into Rag-/- mice induced severe IBD | [143] |
Il10-/-/Vdr-/- | Spontaneous | NA | NA | NA | ND | Il10-/-/Vdr-/- mice developed more severe IBD compared to IL10-/- mice | [106] |
Il10-/-/Vdr-/- | Spontaneous and Adoptive T cell Transfer | NA | NA | NA | ND | Adoptive transfer of Il10-/-/Vdr-/- CD4 T cells into Rag-/- mice induced severe colitis. Loss of VDR results in decreased T cell homing to the gut and decreased CD4/CD8αα intraepithelial lymphocytes | [89] |
Vdr-/- Il10-/-/Vdr-/-, and Rag-/- | Adoptive T Cell Transfer | NA | NA | NA | ND | Adoptive transfer of Il10-/-/Vdr-/- CD8 T cells into Rag-/- mice induces severe colitis. Vdr-/- CD8 T cells exacerbate CD4/CD45RBhigh cell-induced colitis | [144] |
Strain | Model | Vitamin D metabolite/analog | Dose, route | Treatment window and duration | Serum vit D measure | Outcome | Ref. |
Vitamin D Supplementation | |||||||
A/J | AOM + DSS (3%), 7 d | Ro26-2198 (analog) | 0.01 μg/kg per day, subcutaneous pump | 1 wk prior to AOM | ND | Delayed onset of clinical colitis, decreased cellular proliferation and decreased dysplasia following AOM/DSS | [43] |
CF1 | AOM + DSS (2.5%) × 7 d | D3, 25(OH)D, 1,25(OH)2D3 and 1,25(OH)2D5 | 500 μg D3/kg diet , - 500 μg 25(OH)D/kg diet, 2.5 μg 1,25(OH)2D3/kg diet and 25 μg 1,25(OH)2D5/kg diet | 1 wk prior to AOM + DSS treatment and maintained throughout study | ND | D3, 25(OH)D, and 1,25(OH)2D5 significantly decreased tumor incidence. 1,25(OH)2D3 induced significant weight loss compared to other treatments; not included in final analysis | [118] |
C57BL/6 | AOM + DSS (2%), 4 d × 3 cycles | D3 | 100, 400, 1000, 2500 or 5000 IU/kg diet, diet | 2.5 wk prior to AOM + DSS treatment | 25(OH)D | Vitamin D supplementation significantly decreased dysplasia in a dose dependent manner | [42] |
Smad3-/- | Helicobacter bilis | D3 | 1000 IU or 5000 IU/kg diet, diet | 1 wk prior to infection; maintain throughout study | 25(OH)D | Higher vitamin D significantly decreased tumor incidence | [39] |
Vitamin D Deficiency | |||||||
Smad3-/- | Helicobacter bilis | NA | Vit D deficient diet | 2 wk prior to infection; maintain throughout study | 25(OH)D | No change in dysplasia score or tumor incidence | [39] |
Other (VDR Knockout) | |||||||
Vdr-/- | AOM + DSS (1.5%), 5 d × 3 cycles | NA | NA | NA | ND | Increased inflammation and tumor burdens; increased activation of EGFR and ErbB2 signaling | [145] |
- Citation: Meeker S, Seamons A, Maggio-Price L, Paik J. Protective links between vitamin D, inflammatory bowel disease and colon cancer. World J Gastroenterol 2016; 22(3): 933-948
- URL: https://www.wjgnet.com/1007-9327/full/v22/i3/933.htm
- DOI: https://dx.doi.org/10.3748/wjg.v22.i3.933