Vitamin D receptor pathway is required for probiotic protection in colitis

Shaoping Wu, Sonia Yoon, Yong Guo Zhang, Rong Lu, Yinglin Xia, Jiandi Wan, Elaine O. Petrof, Erika C. Claud, Di Chen, Jun Sun

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Low expression of vitamin D receptor (VDR) and dysfunction of vitamin D/VDR signaling are reported in patients with inflammatory bowel disease (IBD), therefore, restoration of VDR function to control inflammation in IBD is desirable. Probiotics have been used in the treatment of IBD. However, the roleof probiotics in the modulation of VDR signaling to effectively reduce inflammation is unknown. We identified a novel role of probiotics in activating VDR activity, thus inhibiting inflammation, using cell models and VDR knockout mice. We found that the probiotics Lactobacillus rhamnosus strain GG (LGG) and Lactobacillus plantarum (LP) increased VDR protein expression in both mouse and human intestinal epithelial cells. Using the VDR luciferase reporter vector, we detected increased transcriptional activity of VDR after probiotic treatment. Probiotics increased the expression of the VDR target genes, such as antimicrobial peptide cathelicidin, at the transcriptional level. Furthermore, the role of probiotics in regulating VDR signaling was tested in vivo using a Salmonella-colitis model in VDR knockout mice. Probiotic treatment conferred physiological and histologic protection from Salmonella-induced colitis in VDR+/+ mice, whereas probiotics had no effects in the VDR-/- mice. Probiotic treatment also enhanced numbers of Paneth cells, which secrete AMPs for host defense. These data indicate that the VDR pathway is required for probiotic protection in colitis. Understanding how probiotics enhance VDR signaling and inhibit inflammation will allow probiotics to be used effectively, resulting in innovative approaches to the prevention and treatment of chronic inflammation.

Original languageEnglish (US)
Pages (from-to)G341-G349
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume309
Issue number5
DOIs
StatePublished - Sep 4 2015

Keywords

  • AMP
  • Antimicrobial peptide
  • IBD
  • Inflammatory bowel disease
  • Lactobacillus plantarum
  • Lactobacillus rhamnosus strain GG
  • Probiotics
  • Salmonella
  • VDR
  • Vitamin D
  • Vitamin D receptor

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  • Cite this

    Wu, S., Yoon, S., Zhang, Y. G., Lu, R., Xia, Y., Wan, J., Petrof, E. O., Claud, E. C., Chen, D., & Sun, J. (2015). Vitamin D receptor pathway is required for probiotic protection in colitis. American Journal of Physiology - Gastrointestinal and Liver Physiology, 309(5), G341-G349. https://doi.org/10.1152/ajpgi.00105.2015