Vitamin D3 eradicates Helicobacter pylori by inducing VDR-CAMP signaling

Abstract

Background: Vitamin D₃ [VitD₃, 1,25 (OH)₂D₃] is known to have immunomodulatory and anti-microbial properties; however, its activity against Helicobacter pylori is unclear. In this study, we established H. pylori infection models in wild-type and VitD₃ receptor (VDR) knockdown mice and analyzed the effects of VitD₃ and their underlying mechanisms.

Methods: VDR^+/+ and VDR^+/- mice were intragastrically infected with the H. pylori SS1 strain. After confirmation of H. pylori infection, mice were treated with different doses of VitD₃. The infection levels in stomach tissues were quantified using the colony-forming assay, and the expression levels of the VDR and cathelicidin antimicrobial peptide (CAMP) in the gastric mucosa were analyzed by immunohistochemistry and western blotting.

Results: The gastric mucosa of VDR^+/- mice was more susceptible to H. pylori colonization and had lower levels of VDR and CAMP expression than that of VDR^+/+ mice. H. pylori infection upregulated VDR and CAMP expression in the stomach of both wild-type and mutant mice, and VitD₃ treatment resulted in further increase of VDR and CAMP levels, while significantly and dose-dependently decreasing the H. pylori colonization rate in both mouse groups, without affecting blood calcium or phosphorus levels.

Conclusion: Our data indicate that oral administration of VitD₃ reduces the H. pylori colonization rate and upregulates VDR and CAMP expression in the gastric mucosa, suggesting a role for VitD₃/VDR/CAMP signaling in the eradication of H. pylori in the stomach. These findings provide important insights into the mechanism underlying the anti-H. pylori activity of VitD₃ and should be useful in the development of measures to eradicate H. pylori.

Keywords: 1α; 25-dihydroxyvitamin D3; H. pylori; cathelicidin antimicrobial peptide; inflammation; vitamin D receptor.