Lacking vitamin D receptor leads to intestinal dysbiosis

Abstract

The microbiome modulates numerous aspects of human physiology and is critical in development of diseases. Vitamin D and its receptor VDR are associated with various diseases. We hypothesize that VDR status alters the composition and functions of microbiota. Fecal and cecal stool samples were harvested from VDR knockout mice and intestinal epithelial VDR conditional knockout (VDRΔIEC) mice. After 454 pyrosequencing, the sequences were clustered into OTUs. PICRUSt, together with HUMAnN were used to analyze the metagenomics and to compare abundances of genes involved in metabolic pathways by reference to KEGG and Clusters of Orthologous Groups databases. In VDR‐/‐ KO mice, Lactobacillus was depleted in fecal stool, whereas Clostridium and Bacteroides were enriched. In cecal stool, Alistipes and Odoribacter were depleted, and Eggerthella was enriched. A comparison between WT and VDR‐/‐ revealed 72 (41 enriched, 31 depleted) and 40 (26 enriched, 14 depleted) functional modules that were significantly altered in fecal and cecal microbiome, respectively. VDRΔIEC mice had enriched Eubacterium, Allobaculum, Prevotella, Limbacter, Anaplasma and depleted Akkermansia in fecal stool, and enriched Roseburia, Pseudoflavonifractor, Allobaculum, Prevotella, Alistipes and Eggerthella, and depleted Lactobacillus and Streptomyces in cecal stool. The numbers of functional modules significantly altered were 75 (33 enriched, 42 depleted) and 89 (47 enriched, 42 depleted) in fecal and cecal microbiome, respectively. Functional alterations regarded synthesis/metabolism of amino acids, carbohydrates and fatty acids, detoxification, infection, and cancer. Effects of VDR in maintaining host‐microbe interactions are critical for intestinal homeostasis. The insights can be exploited to develop novel strategies by restoring VDR in illness.