title: Vitamin D receptor pathway is required for probiotic protection in colitis.
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 role of 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.
authors.affiliation: Department of Biochemistry, Rush University, Chicago, Illinois;
authors.forename: Shaoping
authors.initials: S
authors.lastname: Wu
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York;
authors.forename: Sonia
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry, Rush University, Chicago, Illinois;
authors.forename: Yong-Guo
authors.initials: YG
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Rush University, Chicago, Illinois;
authors.forename: Rong
authors.initials: R
authors.lastname: Lu
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York;
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Microsystems Engineering, Rochester Institute of Technology, Rochester, New York;
authors.forename: Jiandi
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Medicine, Gastrointestinal Diseases Research Unit and Division of Infectious Diseases, Queen's University, Kingston, Ontario, Canada; and.
authors.forename: Elaine O
authors.initials: EO
authors.lastname: Petrof
authors.affiliation: Departments of Pediatrics and Medicine, The University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Claud
authors.affiliation: Department of Biochemistry, Rush University, Chicago, Illinois;
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, Rush University, Chicago, Illinois; jun_sun@rush.edu.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0001-7465-3133
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D048191:Lactiplantibacillus plantarum; D052201:Lacticaseibacillus rhamnosus; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D019879:Paneth Cells / Q000187:drug effects / Q000378:metabolism; D019936:Probiotics / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D018167:Receptors, Calcitriol
keywords: AMP; IBD; Lactobacillus plantarum; Lactobacillus rhamnosus strain GG; Salmonella; VDR; antimicrobial peptide; inflammatory bowel disease; probiotics; vitamin D; vitamin D receptor