title: Lack of Vitamin D Receptor Causes Dysbiosis and Changes the Functions of the Murine Intestinal Microbiome.
abstract: OBJECTIVE
  The microbiome modulates numerous aspects of human physiology and is a crucial factor in the development of various human diseases. Vitamin D deficiency and downregulation of the vitamin D receptor (VDR) are also associated with the pathogenesis of diseases such as inflammatory bowel disease, cancers, obesity, diabetes, and asthma. VDR is a nuclear receptor that regulates the expression of antimicrobial peptides and autophagy regulator ATG16L1. Vitamin D may promote a balanced intestinal microbiome and improve glucose homeostasis in diabetes. However, how VDR regulates microbiome is not well known. In the current study, we hypothesize that VDR status regulates the composition and functions of the intestinal bacterial community.
  
  
  METHODS
  Fecal and cecal stool samples were harvested from Vdr knockout (Vdr(-/-)) and wild-type mice for bacterial DNA and then sequenced with 454 pyrosequencing. The sequences were denoised and clustered into operational taxonomic units, then queried against the National Center for Biotechnology Information database. Metagenomics were analyzed, and the abundances of genes involved in metabolic pathways were compared by reference to the Kyoto Encyclopedia of Genes and Genomes and Clusters of Orthologous Groups databases.
  
  
  RESULTS
  In the Vdr(-/-) mice, Lactobacillus was depleted in the fecal stool, whereas Clostridium and Bacteroides were enriched. Bacterial taxa along the Sphingobacteria-to-Sphingobacteriaceae lineage were enriched, but no genera reached statistical significance. In the cecal stool, Alistipes and Odoribacter were depleted, and Eggerthella was enriched. Notably, all of the taxa upstream of Eggerthella remained unchanged. A comparison of Vdr(-/-) and wild-type samples revealed 40 (26 enriched, 14 depleted) and 72 (41 enriched, 31 depleted) functional modules that were significantly altered in the cecal and fecal microbiomes, respectively (both, P < 0.05), due to the loss of Vdr. In addition to phylogenetic differences in gut microbiome with different intestinal origins, we identify several important pathways, such as nucleotide-binding oligomerization domain-like receptor, affected by Vdr status, including amino acid, carbohydrate, and fatty acid synthesis and metabolism, detoxification, infections, signal transduction, and cancer and other diseases.
  
  
  CONCLUSIONS
  Our study fills knowledge gaps by having investigated the microbial profile affected by VDR. Insights from our findings can be exploited to develop novel strategies to treat or prevent various diseases by restoring VDR function and healthy microbe-host interactions.
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, Illinois.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Jin
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, Illinois.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, Illinois.
authors.forename: Yong-Guo
authors.initials: YG
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Rush University Medical Center, 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: Department of Gastroenterology, Xingqiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, Illinois. Electronic address: jun_sun@rush.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D002432:Cecum / Q000382:microbiology; D015536:Down-Regulation; D064806:Dysbiosis / Q000503:physiopathology*; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D007422:Intestines / Q000382:microbiology; D008297:Male; D018345:Mice, Knockout; D010802:Phylogeny; D018167:Receptors, Calcitriol / Q000172:deficiency* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D018167:Receptors, Calcitriol
keywords: Bacteroides; Clostridium; NOD-like receptor; dysbiosis; immunity; inflammation; intestine; microbiome; vitamin D; vitamin D receptor