1,25(OH)2D3 deficiency-induced gut microbial dysbiosis degrades the colonic mucus barrier in Cyp27b1 knockout mouse model

Wenjing Zhu,Qianwen Zhou,Jiayao Yan,Chunchun Zhi,Xiaoqin Yuan

doi:10.1186/s13099-019-0291-z

Abstract

BackgroundThe relationship between disturbances of the gut microbiota and 1,25(OH)2D3 deficiency has been established both in humans and animal models with a vitamin D poor diet or a lack of sun exposure. Our prior study has demonstrated that Cyp27b1−/− (Cyp27b1 knockout) mice that could not produce 1,25(OH)2D3 had significant colon inflammation phenotypes. However, whether and how 1,25(OH)2D3 deficiency due to the genetic deletion controls the gut homeostasis and modulates the composition of the gut microbiota remains to be explored.Results1,25(OH)2D3 deficiency impair the composition of the gut microbiota and metabolite in Cyp27b1−/− mice, including Akkermansia muciniphila, Solitalea Canadensis, Bacteroides-acidifaciens, Bacteroides plebeius and SCFA production. 1,25(OH)2D3 deficiency cause the thinner colonic mucus layer and increase the translocation of the bacteria to the mesenteric lymph nodes. We also found 1,25(OH)2D3 supplement significantly decreased Akkermansia muciniphila abundance in fecal samples of Cyp27b1−/− mice.ConclusionDeficiency in 1,25(OH)2D3 impairs the composition of gut microbiota leading to disruption of intestinal epithelial barrier homeostasis and induction of colonic inflammation. This study highlights the association between 1,25(OH)2D3 status, the gut microbiota and the colonic mucus barrier that is regarded as a primary defense against enteric pathogens.

Highlights

The relationship between disturbances of the gut microbiota and 1,25(OH)2D3 deficiency has been established both in humans and animal models with a vitamin D poor diet or a lack of sun exposure
Effects of 1,25(OH)2D3 deficiency on gut microbiota Having demonstrated that the composition of the gut microbiota was dependent on 1,25(OH)2D3, we examined whether bacterial populations in WT mice were different from those in Cyp27b1−/− mice by 16S rRNA sequencing of bacterial DNA extracted from the feces of these mice
Statistical analysis revealed that Akkermansia muciniphila (A. muciniphila) and Solitalea canadensis were more abundant in Cyp27b1−/− mice, especially A. muciniphila being affected to an even higher extent in Cyp27b1−/− mice (Fig. 2b)

Summary

Introduction

The relationship between disturbances of the gut microbiota and 1,25(OH)2D3 deficiency has been established both in humans and animal models with a vitamin D poor diet or a lack of sun exposure. In addition to its role in regulating Ca2+ and Pi transport and bone mineralization, 1,25(OH)2D3 possesses various biological activities through binding vitamin D receptor (VDR), a high-affinity nuclear receptor that transcriptionally regulates its target genes [2]. 1,25(OH)2D3 deficiency or VDR knockout increased the risk of colitis [9,10,11]. Vitamin D might play a protective role for IBD. The role vitamin D plays in the pathogenesis of IBD is complex and not well defined. Some investigations have shown that 1,25(OH)2D3 has a pivotal role in the development of IBD via regulating innate and adaptive immune response [13], autophagy [14] or gut barrier

Methods

Results

Discussion

Conclusion