AUTHOR=Zhang Ye , Wang Chunya , Zhang Li , Yu Jie , Yuan Wenjie , Li Lei 

TITLE=Vitamin D3 eradicates Helicobacter pylori by inducing VDR-CAMP signaling

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1033201

DOI=10.3389/fmicb.2022.1033201

ISSN=1664-302X

ABSTRACT=<sec><title>Background</title><p>Vitamin D<sub>3</sub> [VitD<sub>3</sub>, 1,25 (OH)<sub>2</sub>D<sub>3</sub>] is known to have immunomodulatory and anti-microbial properties; however, its activity against <italic>Helicobacter pylori</italic> is unclear. In this study, we established <italic>H. pylori</italic> infection models in wild-type and VitD<sub>3</sub> receptor (VDR) knockdown mice and analyzed the effects of VitD<sub>3</sub> and their underlying mechanisms.</p></sec><sec><title>Methods</title><p>VDR<sup>+/+</sup> and VDR<sup>+/–</sup> mice were intragastrically infected with the <italic>H. pylori</italic> SS1 strain. After confirmation of <italic>H. pylori</italic> infection, mice were treated with different doses of VitD<sub>3</sub>. 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.</p></sec><sec><title>Results</title><p>The gastric mucosa of VDR<sup>+/–</sup> mice was more susceptible to <italic>H. pylori</italic> colonization and had lower levels of VDR and CAMP expression than that of VDR<sup>+/+</sup> mice. <italic>H. pylori</italic> infection upregulated VDR and CAMP expression in the stomach of both wild-type and mutant mice, and VitD<sub>3</sub> treatment resulted in further increase of VDR and CAMP levels, while significantly and dose-dependently decreasing the <italic>H. pylori</italic> colonization rate in both mouse groups, without affecting blood calcium or phosphorus levels.</p></sec><sec><title>Conclusion</title><p>Our data indicate that oral administration of VitD<sub>3</sub> reduces the <italic>H. pylori</italic> colonization rate and upregulates VDR and CAMP expression in the gastric mucosa, suggesting a role for VitD<sub>3</sub>/VDR/CAMP signaling in the eradication of <italic>H. pylori</italic> in the stomach. These findings provide important insights into the mechanism underlying the anti-<italic>H. pylori</italic> activity of VitD<sub>3</sub> and should be useful in the development of measures to eradicate <italic>H. pylori</italic>.</p></sec>