A healthy gut needs Vitamin D and a good vitamin D receptor

Created September 2022

Many gut studies are unaware of the importance of

  • Vitamin D Receptor - which can limit vitamin D getting to cells

  • Vitamin D Receptor activators

  • Gut-friendly forms of Vitamin D

  • Gut biome -which can increase response to vitamin D

Vitamin D and Gut Health

Adv Exp Med Biol. 2022;1390:155-167.doi: 10.1007/978-3-031-11836-4_9   PDF is behind $30 paywall

James C Fleet 1

Vitamin D is a conditionally required nutrient that can either be obtained from skin synthesis following UVB exposure from the diet. Once in the body, it is metabolized to produce the endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)2D), that regulates gene expression in target tissues by interacting with a ligand-activated transcription factor, the vitamin D receptor ( VDR ). The first, and most responsive, vitamin D target tissue is the intestine. The classical intestinal role for vitamin D is the control of calcium metabolism through the regulation of intestinal calcium absorption. However, studies clearly show that other functions of the intestine are regulated by the molecular actions of 1,25(OH)2 D that are mediated through the VDR . This includes enhancing gut barrier function, regulation of intestinal stem cells, suppression of colon carcinogenesis, and inhibiting intestinal inflammation. While research demonstrates that there are both classical, calcium-regulating and non-calcium regulating roles for vitamin D in the intestine, the challenge facing biomedical researchers is how to translate these findings in ways that optimize human intestinal health.

VitaminDWiki - studies in both categories Gut and VDR

This list is automatically updated

{category}

VitaminDWiki - Overview Gut and vitamin D contains

{include}

VitaminDWiki - (Overview Gut and vitamin D)) contains gut-friendly information

{include}

VitaminDWiki - studies in both categories Microbiome and Gut

{category}

VitaminDWiki - Vitamin D Receptor activation can be increased in 14 ways

Omega-3,  Magnesium,  Zinc,   Quercetin,   non-daily Vit D,  Curcumin, intense exercise, Butyrate- in Gut   Ginger,   Essential oils, etc  Note: The founder of VitaminDWiki uses 10 of the 14 known VDR activators

PDF References

  1. Nicolaysen R (1937) Studies upon the mode of action of Vitamin D. The influence of vitamin D on the absorption of calcium and phosphorus in the rat. Biochem J 37:122–129 - DOI

  2. Pansu D, Bellaton C, Roche C, Bronner F (1983) Duodenal and ileal calcium absorption in the rat and effects of vitamin D. Am J Phys 244(6):G695–G700

  3. Sheikh MS, Ramirez A, Emmett M, Santa AC, Schiller LR, Fordtran JS (1988) Role of vitamin D-dependent and vitamin D-independent mechanisms in absorption of food calcium. J Clin Invest 81(1):126–132 - PubMed - PMC - DOI

  4. Holick MF, Schnoes HK, DeLuca HF, Suda T, Cousins RJ (1971) Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine. Biochemistry 10(14):2799–2804 - PubMed - DOI

  5. Norman AW, Myrtle JF, Midgett RJ, Nowicki HG, Williams V, Popjak G (1971) 1,25-dihydroxycholecalciferol: identification of the proposed active form of vitamin D3 in the intestine. Science 173(3991):51–54 - PubMed - DOI

  6. Brumbaugh PF, Haussler MR (1973) Nuclear and cytoplasmic receptor s for 1,25-dihydroxycholecalciferol in intestinal mucosa. Biochem Biophys Res Commun 51(1):74–80 - PubMed - DOI

  7. Carlberg C (2017) Molecular endocrinology of vitamin D on the epigenome level. Mol Cell Endocrinol 453:14–21 - PubMed - DOI

  8. Pike JW, Meyer MB (2014) Fundamentals of vitamin D hormone-regulated gene expression. J Steroid Biochem Mol Biol 144(Pt A):5–11 - PubMed - DOI

  9. Lee SM, Bishop KA, Goellner JJ, O’Brien CA, Pike JW (2014) Mouse and human BAC transgenes recapitulate tissue-specific expression of the vitamin D receptor in mice and rescue the VDR -null phenotype. Endocrinology 155(6):2064–2076 - PubMed - PMC - DOI

  10. Cartwright JA, Gow AG, Milne E et al (2018) Vitamin D receptor expression in dogs. J Vet Intern Med 32(2):764–774 - PubMed - PMC - DOI

  11. Walters MR (1992) Newly identified actions of the vitamin D endocrine system. Endocr Rev 13(4):719–764 - PubMed

  12. Massaro E, Simpson R, DeLuca H (1983) Quantification of endogenously occupied and unoccupied binding sites for 1,25 dihydroxyvitamin D3 in rat intestine. Proc Natl Acad Sci U S A 80:2549–2553 - PubMed - PMC - DOI

  13. Liel Y, Shany S, Smirnoff P, Schwartz B (1999) Estrogen increases 1,25-dihydroxyvitamin D receptor s expression and bioresponse in the rat duodenal mucosa. Endocrinology 140(1):280–285 - PubMed - DOI

  14. Pierce EA, DeLuca HF (1988) Regulation of the intestinal 1,25-dihydroxyvitamin D3 receptor during neonatal development in the rat. Arch Biochem Biophys 261:241–249 - PubMed - DOI

  15. Takamoto S, Seino Y, Sacktor B, Liang CT (1990) Effect of age on duodenal 1,25-dihydroxyvitamin D-3 receptor s in Wistar rats. Biochim Biophys Acta 1034:22–28 - PubMed - DOI

  16. Horst RL, Goff JP, Reinhardt TA (1990) Advancing age results in reduction of intestinal and bone 1,25 dihydroxyvitamin D receptor . Endocrinology 126:1053–1057 - PubMed - DOI

  17. Van Cromphaut SJ, Dewerchin M, Hoenderop JG et al (2001) Duodenal calcium absorption in vitamin D receptor -knockout mice: functional and molecular aspects. Proc Natl Acad Sci U S A 98(23):13324–13329 - PubMed - PMC - DOI

  18. Song Y, Kato S, Fleet JC (2003) Vitamin D receptor ( VDR ) knockout mice reveal VDR -independent regulation of intestinal calcium absorption and ECaC2 and calbindin D9k mRNA. J Nutr 133(2):374–380 - PubMed - DOI

  19. Lieben L, Masuyama R, Torrekens S et al (2012) Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. J Clin Invest 122(5):1803–1815 - PubMed - PMC - DOI

  20. Xue YB, Fleet JC (2009) Intestinal Vitamin D receptor is required for Normal calcium and bone metabolism in mice. Gastroenterology 136(4):1317–1327 - PubMed - DOI

  21. Wasserman RH, Taylor AN (1969) Some aspects of the intestinal absorption of calcium, with special reference to vitamin D. In: Comar CL, Bronner F (eds) Mineral metabolism, an advanced treatise. 3. Academic, New York, pp 321–403

  22. Pansu D, Bellaton C, Bronner F (1981) Effect of Ca intake on saturable and nonsaturable components of duodenal Ca transport. Am J Phys 240(1):32–37

  23. Heaney RP, Saville PD, Recker RR (1975) Calcium absorption as a function of calcium intake. J Lab Clin Med 85(6):881–890 - PubMed

  24. Sheikh MS, Schiller LR, Fordtran JS (1990) In vivo intestinal absorption of calcium in humans. Miner Electrolyte Metab 16(2–3):130–146 - PubMed

  25. Chandra S, Fullmer CS, Smith CA, Wasserman RH, Morrison GH (1990) Ion microscopic imaging of calcium transport in the intestinal tissue of vitamin D-deficient and vitamin D-replete chickens: a 44Ca stable isotope study. Proc Natl Acad Sci U S A 87(15):5715–5719 - PubMed - PMC - DOI

  26. Fullmer CS, Chandra S, Smith CA, Morrison GH, Wasserman RH (1996) Ion microscopic imaging of calcium during 1,25-dihydroxyvitamin D-mediated intestinal absorption. Histochem Cell Biol 106(2):215–222 - PubMed - DOI

  27. Giuliano AR, Wood RJ (1991) Vitamin D-regulated calcium transport in Caco-2 cells: unique in vitro model. Am J Phys 260(2 Pt 1):G207–GG12

  28. Favus MJ, Angeid-Backman E, Breyer MD, Coe FL (1983) Effects of trifluoperazine,ouabain, and ethacrynic acid on intestinal calcium. Am J Phys 244:G111–G1G5

  29. Favus MJ, Kathpalia SC, Coe FL (1981) Kinetic characteristics of calcium absorption and secretion by rat colon. Am J Phys 240(5):G350–G3G4

  30. Favus MJ, Langman CB (1984) Effects of 1,25 dihydroxyvitamin D3 on colonic calcium transport in vitamin D-deficient and normal rats. Am J Phys 246:G268–GG73

  31. Karbach U, Rummel W (1987) Calcium transport across the colon ascendens and the influence of 1,25-dihydroxyvitamin D3 and dexamethasone. Eur J Clin Invest 17(4):368–374 - PubMed - DOI

  32. Karbach U, Feldmeier H (1993) The cecum is the site with the highest calcium absorption in rat intestine. Dig Dis Sci 38(10):1815–1824 - PubMed - DOI

  33. Barger-Lux MJ, Heaney RP, Recker RR (1989) Time course of calcium absorption in humans: evidence for a colonic component. Calcif Tissue Int 44(5):308–311 - PubMed - DOI

  34. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G (2016) Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev 96(1):365–408 - PubMed - DOI

  35. Reyes-Fernandez PC, Fleet JC (2016) Compensatory changes in calcium metabolism accompany the loss of Vitamin D receptor ( VDR ) from the distal intestine and kidney of mice. J Bone Miner Res 31(1):143–151 - PubMed - DOI

  36. Fleet JC (2018) Regulation of intestinal calcium and phosphate absorption. In: JWP DF, Bouillon R, Giovannucci E, Goltzman D, Hewison M (eds) Vitamin D. 1, 4th edn. Academic, pp 329–342 - DOI

  37. Bronner F, Pansu D, Stein WD (1986) An analysis of intestinal calcium transport across the rat intestine. Am J Phys 250(5 Pt 1):G561–G5G9

  38. Peng JB, Chen XZ, Berger UV et al (1999) Molecular cloning and characterization of a channel-like transporter mediated intestinal calcium absorption. J Biol Chem 274:22739–22746 - PubMed - DOI

  39. Meyer MB, Zella LA, Nerenz RD, Pike JW (2007) Characterizing early events associated with the activation of target genes by 1,25-dihydroxyvitamin D3 in mouse kidney and intestine in vivo. J Biol Chem 282:22344–22352 - PubMed - DOI

  40. Fleet JC, Eksir F, Hance KW, Wood RJ (2002) Vitamin D-inducible calcium transport and gene expression in three Caco-2 cell lines. Am J Phys 283(3):G618–GG25

  41. Song Y, Peng X, Porta A et al (2003) Calcium transporter 1 and epithelial calcium channel messenger ribonucleic acid are differentially regulated by 1,25 dihydroxyvitamin D3 in the intestine and kidney of mice. Endocrinology 144(9):3885–3894 - PubMed - DOI

  42. Kutuzova GD, Sundersingh F, Vaughan J et al (2008) TRPV6 is not required for 1alpha,25-dihydroxyvitamin D3-induced intestinal calcium absorption in vivo. Proc Natl Acad Sci U S A 105(50):19655–19659 - PubMed - PMC - DOI

  43. Benn BS, Ajibade D, Porta A et al (2008) Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k. Endocrinology 149(6):3196–3205 - PubMed - PMC - DOI

  44. Woudenberg-Vrenken TE, Lameris AL, Weissgerber P et al (2012) Functional TRPV6 channels are crucial for transepithelial Ca2+ absorption. Am J Physiol Gastrointest Liver Physiol 303(7):G879–G885 - PubMed - DOI

  45. Cui M, Li Q, Johnson R, Fleet JC (2012) Villin promoter-mediated transgenic expression of transient receptor potential cation channel, subfamily V, member 6 (TRPV6) increases intestinal calcium absorption in wild-type and vitamin D receptor knockout mice. J Bone Miner Res 27(10):2097–2107 - PubMed - DOI

  46. Akhter S, Kutuzova GD, Christakos S, DeLuca HF (2007) Calbindin D9k is not required for 1,25-dihydroxyvitamin D3-mediated Ca2+ absorption in small intestine. Arch Biochem Biophys 460(2):227–232 - PubMed - DOI

  47. Spencer R, Charman M, Wilson PW, Lawson DEM (1978) The relationship between vitamin D-stimulated calcium transport and intestinal calcium-binding protein in the chicken. Biochem J 170:93–101 - PubMed - PMC - DOI

  48. Wasserman RH, Smith CA, Brindak ME et al (1992) Vitamin-D and mineral deficiencies increase the plasma membrane calcium pump of chicken intestine. Gastroenterology 102(3):886–894 - PubMed - DOI

  49. Cai Q, Chandler JS, Wasserman RH, Kumar R, Penniston JT (1993) Vitamin D and adaptation to dietary calcium and phosphate deficiencies increase intestinal plasma membrane calcium pump gene expression. Proc Natl Acad Sci U S A 90(4):1345–1349 - PubMed - PMC - DOI

  50. Liu C, Weng H, Chen L et al (2013) Impaired intestinal calcium absorption in protein 4.1R-deficient mice due to altered expression of plasma membrane calcium ATPase 1b (PMCA1b). J Biol Chem 288(16):11407–11415 - PubMed - PMC - DOI

  51. Ryan ZC, Craig TA, Filoteo AG et al (2015) Deletion of the intestinal plasma membrane calcium pump, isoform 1, Atp2b1, in mice is associated with decreased bone mineral density and impaired responsiveness to 1, 25-dihydroxyvitamin D3. Biochem Biophys Res Commun 467(1):152–156 - PubMed - PMC - DOI

  52. Davis WL, Jones RG (1982) Lysosomal proliferation in rachitic avian intestinal absorptive cells following 1,25-dihydroxycholecalciferol. Tissue Cell 14:585–595 - PubMed - DOI

  53. Nemere I, Szego CM (1981) Early actions of parathyroid hormone and 1,25-dihydroxycholecalciferol on isolated epithelial cells from rat intestine: 1. Limited lysosomal enzyme release and calcium uptake. Endocrinology 108:1450–1462 - PubMed - DOI

  54. Warner RR, Coleman JR (1975) Electron probe analysis of calcium transport by small intestine. J Cell Biol 64(1):54–74 - PubMed - DOI

  55. Nemere I, Leathers V, Norman AW (1986) 1, 25 dihydroxyvitamin D3-mediated intestinal calcium transport. Biochemical identification of lysozomes containing calcium and calcium-binding protein (calbindin-D 28k ). J Biol Chem 261:16106–16114 - PubMed - DOI

  56. Nemere I, Yoshimoto Y, Norman AW (1984) Calcium transport in perfused duodena from normal chicks: enhancement within fourteen minutes of exposure to 1,25 dihydroxyvitamin D3. Endocrinology 115:1476–1483 - PubMed - DOI

  57. Huhtakangas JA, Olivera CJ, Bishop JE, Zanello LP, Norman AW (2004) The vitamin D receptor is present in caveolae-enriched plasma membranes and binds 1 alpha,25(OH)(2)-vitamin D-3 in vivo and in vitro. Mol Endocrinol 18(11):2660–2671 - PubMed - DOI

  58. Nemere I, Safford SE, Rohe B, DeSouza MM, Farach-Carson MC (2004) Identification and characterization of 1,25D(3)-membrane-associated rapid response, steroid (1,25D(3)-MARRS) binding protein. J Steroid Biochem Mol Biol 89–90:281–285 - PubMed - DOI

  59. Nemere I, Garbi N, Hammerling GJ, Khanal RC (2010) Intestinal cell calcium uptake and the targeted knockout of the 1,25D3-MARRS (membrane-associated, rapid response steroid-binding) receptor /PDIA3/Erp57. J Biol Chem 285(41):31859–31866 - PubMed - PMC - DOI

  60. Nemere I, Garcia-Garbi N, Hammerling GJ, Winger Q (2012) Intestinal cell phosphate uptake and the targeted knockout of the 1,25D(3)-MARRS receptor /PDIA3/ERp57. Endocrinology 153(4):1609–1615 - PubMed - DOI

  61. Nemere I, Garbi N, Hammerling G, Hintze KJ (2012) Role of the 1,25D(3)-MARRS receptor in the 1,25(OH)(2)D(3)-stimulated uptake of calcium and phosphate in intestinal cells. Steroids 77(10):897–902 - PubMed - DOI

  62. Karbach U (1992) Paracellular calcium transport across the small intestine. J Nutr 122(3):672–677 - PubMed - DOI

  63. Tudpor K, Teerapornpuntakit J, Jantarajit W, Krishnamra N, Charoenphandhu N (2008) 1,25-dihydroxyvitamin d(3) rapidly stimulates the solvent drag-induced paracellular calcium transport in the duodenum of female rats. J Physiol Sci 58(5):297–307 - PubMed - DOI

  64. Fujita H, Sugimoto K, Inatomi S et al (2008) Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Mol Biol Cell 19(5):1912–1921 - PubMed - PMC - DOI

  65. Reyes Fernandez PC, Replogle RA, Wang L, Zhang M, Fleet JC (2016) Novel genetic loci control calcium absorption and femur bone mass as well as their response to low calcium intake in male BXD recombinant inbred mice. J Bone Miner Res 31(5):994–1002 - PubMed - DOI

  66. Sitrin M, Meredith S, Rosenberg IH (1978) Vitamin D deficiency and bone disease in gastrointestinal disorders. Arch Intern Med 138(Suppl_5):886–888 - PubMed - DOI

  67. Schachter D, Finkelstein JD, Kowarski S (1964) Metabolism of Vitamin D. I. Preparation of radioactive Vitamin D and its intestinal absorption in the rat. J Clin Invest 43:787–796 - PubMed - PMC - DOI

  68. Hollander D (1981) Intestinal absorption of vitamins A, E, D, and K. J Lab Clin Med 97(4):449–462 - PubMed

  69. Dueland S, Pedersen JI, Helgerud P, Drevon CA (1983) Absorption, distribution, and transport of vitamin D3 and 25-hydroxyvitamin D3 in the rat. Am J Phys 245(5 Pt 1):E463–E467

  70. Sitrin MD, Pollack KL, Bolt MJ, Rosenberg IH (1982) Comparison of vitamin D and 25-hydroxyvitamin D absorption in the rat. Am J Phys 242(4):G326–G332

  71. Watkins DW, Khalafi R, Cassidy MM, Vahouny GV (1985) Alterations in calcium, magnesium, iron, and zinc metabolism by dietary cholestyramine. Dig Dis Sci 30(5):477–482 - PubMed - DOI

  72. Reboul E, Goncalves A, Comera C et al (2011) Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. Mol Nutr Food Res 55(5):691–702 - PubMed - DOI

  73. Khamiseh G, Vaziri ND, Oveisi F, Ahmadnia MR, Ahmadnia L (1991) Vitamin D absorption, plasma concentration and urinary excretion of 25-hydroxyvitamin D in nephrotic syndrome. Proc Soc Exp Biol Med 196(2):210–213 - PubMed - DOI

  74. Krawitt EL, Chastenay BF (1980) 25-hydroxy vitamin D absorption test in patients with gastrointestinal disorders. Calcif Tissue Int 32(3):183–187 - PubMed - DOI

  75. Bikle D (2000) Vitamin D: Production, Metabolism, and Mechanisms of Action. In: Feingold KR, Anawalt B, Boyce A et al (eds) Endotext. South Dartmouth (MA)

  76. Kurogi K, Sakakibara Y, Suiko M, Liu MC (2017) Sulfation of vitamin D3 -related compounds-identification and characterization of the responsible human cytosolic sulfotransferases. FEBS Lett 591(16):2417–2425 - PubMed - DOI

  77. Hashizume T, Xu Y, Mohutsky MA et al (2008) Identification of human UDP-glucuronosyltransferases catalyzing hepatic 1alpha,25-dihydroxyvitamin D3 conjugation. Biochem Pharmacol 75(5):1240–1250 - PubMed - DOI

  78. Larsson SE, Lorentzon R (1977) Excretion of active metabolites of vitamin D in urine and bile of the adult rat. Clin Sci Mol Med 53(4):373–377 - PubMed

  79. Zimmerman DR, Koszewski NJ, Hoy DA, Goff JP, Horst RL (2015) Targeted delivery of 1,25-dihydroxyvitamin D3 to colon tissue and identification of a major 1,25-dihydroxyvitamin D3 glycoside from Solanumglaucophyllum plant leaves. J Steroid Biochem Mol Biol 148:318–325 - PubMed - DOI

  80. Wiesner RH, Kumar R, Seeman E, Go VL (1980) Enterohepatic physiology of 1,25-dihydroxyvitamin D3 metabolites in normal man. J Lab Clin Med 96(6):1094–1100 - PubMed

  81. Kumar R (1984) Metabolism of 1,25-dihydroxyvitamin D3. Physiol Rev 64(2):478–504 - PubMed - DOI

  82. Koszewski NJ, Horst RL, Goff JP (2012) Importance of apical membrane delivery of 1,25-dihydroxyvitamin D3 to vitamin D-responsive gene expression in the colon. Am J Physiol Gastrointest Liver Physiol 303(7):G870–G878 - PubMed - PMC - DOI

  83. Crosnier C, Stamataki D, Lewis J (2006) Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Nat Rev Genet 7(5):349–359 - PubMed - DOI

  84. Wang L, Klopot A, Freund JN, Dowling LN, Krasinski SD, Fleet JC (2004) Control of Differentiation-Induced Calbindin-D 9k Gene Expression in Caco-2 Cells by Cdx-2 adn HNF-1à. Am J Phys 287:G943–G953

  85. Meyer MB, Watanuki M, Kim S, Shevde NK, Pike JW (2006) The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25-dihydroxyvitamin D3 in intestinal cells. Mol Endocrinol 20(6):1447–1461 - PubMed - DOI

  86. Wood RJ, Tchack L, Angelo G, Pratt RE, Sonna LA (2004) DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line. Physiol Genomics 17(2):122–129 - PubMed - DOI

  87. Lee SM, Riley EM, Meyer MB et al (2015) 1,25-Dihydroxyvitamin D3 controls a cohort of Vitamin D receptor target genes in the proximal intestine that is enriched for calcium-regulating components. J Biol Chem 290(29):18199–18215 - PubMed - PMC - DOI

  88. Li S, De La Cruz J, Hutchens S et al (2020) Analysis of 1,25-dihydroxyvitamin D3 genomic action reveals calcium-regulating and calcium-independent effects in mouse intestine and human enteroids. Mol Cell Biol 41(1):e00372-20 - PubMed - PMC - DOI

  89. Barker N, van Es JH, Kuipers J et al (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449(7165):1003–1007 - PubMed - DOI

  90. Barker N, Ridgway RA, van Es JH et al (2009) Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457(7229):608–611 - PubMed - DOI

  91. Peregrina K, Houston M, Daroqui C, Dhima E, Sellers RS, Augenlicht LH (2015) Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions. Carcinogenesis 36(1):25–31 - PubMed - DOI

  92. Costales-Carrera A, Fernandez-Barral A, Bustamante-Madrid P et al (2020) Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue. Cancers (Basel) 12(8):2302 - DOI

  93. Yan KS, Chia LA, Li X et al (2012) The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc Natl Acad Sci U S A 109(2):466–471 - PubMed - DOI

  94. Li W, Zimmerman SE, Peregrina K et al (2019) The nutritional environment determines which and how intestinal stem cells contribute to homeostasis and tumorigenesis. Carcinogenesis 40(8):937–946 - PubMed - PMC - DOI

  95. Sittipo P, Kim HK, Han J, Lee MR, Lee YK (2021) Vitamin D3 suppresses intestinal epithelial stemness via ER stress induction in intestinal organoids. Stem Cell Res Ther 12(1):285 - PubMed - PMC - DOI

  96. Laukoetter MG, Bruewer M, Nusrat A (2006) Regulation of the intestinal epithelial barrier by the apical junctional complex. Curr Opin Gastroenterol 22(2):85–89 - PubMed - DOI

  97. Watson AJ, Chu S, Sieck L et al (2005) Epithelial barrier function in vivo is sustained despite gaps in epithelial layers. Gastroenterology 129(3):902–912 - PubMed - DOI

  98. Kong J, Zhang Z, Musch MW et al (2008) Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. AJP – Gastrointest Liver Physiol 294(1):G208–GG16 - DOI

  99. Zhao H, Zhang H, Wu H et al (2012) Protective role of 1,25(OH)2 vitamin D3 in the mucosal injury and epithelial barrier disruption in DSS-induced acute colitis in mice. BMC Gastroenterol 12:57 - PubMed - PMC - DOI

  100. Chen SW, Wang PY, Zhu J et al (2015) Protective effect of 1,25-dihydroxyvitamin d3 on lipopolysaccharide-induced intestinal epithelial tight junction injury in caco-2 cell monolayers. Inflammation 38(1):375–383 - PubMed - DOI

  101. Froicu M, Cantorna MT (2007) Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury. BMC Immunol 8:5 - PubMed - PMC - DOI

  102. Reich KM, Fedorak RN, Madsen K, Kroeker KI (2014) Vitamin D improves inflammatory bowel disease outcomes: basic science and clinical review. World J Gastroenterol 20(17):4934–4947 - PubMed - PMC - DOI

  103. Wang F, Johnson RL, DeSmet ML, Snyder PW, Fairfax KC, Fleet JC (2017) Vitamin D receptor -dependent signaling protects mice from dextran sulfate sodium-induced colitis. Endocrinology 158(6):1951–1963 - PubMed - PMC - DOI

  104. Brown H, Esterhazy D (2021) Intestinal immune compartmentalization: implications of tissue specific determinants in health and disease. Mucosal Immunol 14(6):1259–1270 - PubMed - DOI

  105. Charoenngam N, Holick MF (2020) Immunologic effects of Vitamin D on human health and disease. Nutrients 12(7):2097 - PMC - DOI

  106. Mailhot G, White JH (2020) Vitamin D and immunity in infants and children. Nutrients 12(5):1233 - PMC - DOI

  107. Prietl B, Treiber G, Pieber TR, Amrein K (2013) Vitamin D and immune function. Nutrients 5(7):2502–2521 - PubMed - PMC - DOI

  108. Ooi JH, McDaniel KL, Weaver V, Cantorna MT (2014) Murine CD8+ T cells but not macrophages express the vitamin D 1alpha-hydroxylase. J Nutr Biochem 25(1):58–65 - PubMed - DOI

  109. Overbergh L, Decallonne B, Valckx D et al (2000) Identification and immune regulation of 25-hydroxyvitamin D-1-alpha-hydroxylase in murine macrophages. Clin Exp Immunol 120(1):139–146 - PubMed - PMC - DOI

  110. Stoffels K, Overbergh L, Giulietti A, Verlinden L, Bouillon R, Mathieu C (2006) Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes. J Bone Miner Res 21(1):37–47 - PubMed - DOI

  111. Hewison M (2010) Vitamin D and the intracrinology of innate immunity. Mol Cell Endocrinol 321(2):103–111 - PubMed - PMC - DOI

  112. Wang TT, Nestel FP, Bourdeau V et al (2004) Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173(5):2909–2912 - PubMed - DOI

  113. Gombart AF, Borregaard N, Koeffler HP (2005) Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J 19(9):1067–1077 - PubMed - DOI

  114. Wang TT, Dabbas B, Laperriere D et al (2010) Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem 285(4):2227–2231 - PubMed - DOI

  115. Lagishetty V, Misharin AV, Liu NQ et al (2010) Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis. Endocrinology 151(6):2423–2432 - PubMed - PMC - DOI

  116. Szeles L, Keresztes G, Torocsik D et al (2009) 1,25-dihydroxyvitamin D3 is an autonomous regulator of the transcriptional changes leading to a tolerogenic dendritic cell phenotype. J Immunol 182(4):2074–2083 - PubMed - DOI

  117. Adams JS, Liu PT, Chun R, Modlin RL, Hewison M (2007) Vitamin D in defense of the human immune response. Ann N Y Acad Sci 1117:94–105 - PubMed - DOI

  118. Mathieu C, van Etten E, Gysemans C et al (2001) In vitro and in vivo analysis of the immune system of vitamin D receptor knockout mice. J Bone Miner Res 16(11):2057–2065 - PubMed - DOI

  119. Yu S, Bruce D, Froicu M, Weaver V, Cantorna MT (2008) Failure of T cell homing, reduced CD4/CD8alphaalpha intraepithelial lymphocytes, and inflammation in the gut of vitamin D receptor KO mice. Proc Natl Acad Sci U S A 105(52):20834–20839 - PubMed - PMC - DOI

  120. Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT (2003) A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol 17(12):2386–2392 - PubMed - DOI

  121. Griffin MD, Dong X, Kumar R (2007) Vitamin D receptor -mediated suppression of RelB in antigen presenting cells: a paradigm for ligand-augmented negative transcriptional regulation. Arch Biochem Biophys 460(2):218–226 - PubMed - PMC - DOI

  122. Palmer MT, Lee YK, Maynard CL et al (2011) Lineage-specific effects of 1,25-dihydroxyvitamin D(3) on the development of effector CD4 T cells. J Biol Chem 286(2):997–1004 - PubMed - DOI

  123. Fletcher J, Cooper SC, Ghosh S, Hewison M (2019) The role of Vitamin D in inflammatory bowel disease: mechanism to management. Nutrients 11(5):1019 - PMC - DOI

  124. Chen J, Waddell A, Lin YD, Cantorna MT (2015) Dysbiosis caused by vitamin D receptor deficiency confers colonization resistance to Citrobacter rodentium through modulation of innate lymphoid cells. Mucosal Immunol 8(3):618–626 - PubMed - DOI

  125. Konya V, Czarnewski P, Forkel M et al (2018) Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells. J Allergy Clin Immunol 141(1):279–292 - PubMed - DOI

  126. He L, Zhou M, Li YC (2019) Vitamin D/Vitamin D receptor signaling is required for normal development and function of group 3 innate lymphoid cells in the Gut. iScience 17:119–131 - PubMed - PMC - DOI

  127. Lin YD, Arora J, Diehl K, Bora SA, Cantorna MT (2019) Vitamin D is required for ILC3 derived IL-22 and protection from Citrobacter rodentium infection. Front Immunol 10:1 - PubMed - PMC - DOI

Tags: Gut Vit D Receptor