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

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

doi:10.1186/s13099-019-0291-z

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

Gut Pathog. 2019 Feb 20:11:8. doi: 10.1186/s13099-019-0291-z. eCollection 2019.

Authors

Wenjing Zhu^#¹, Jiayao Yan^#², Chunchun Zhi³, Qianwen Zhou¹, Xiaoqin Yuan^{1

4}

Affiliations

¹ 1Department of Anatomy, Histology and Embryology, Nanjing Medical University, Xuehai Building, Rm D509, 101 Longmian Avenue, Jiangning District, Nanjing, 211166 China.
² 2Department of Clinical Medicine, First Clinical Medicine College, Nanjing Medical University, Nanjing, 211166 China.
³ 4Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002 China.
⁴ 3Key Laboratory for Aging & Disease, Nanjing Medical University, Nanjing, 211166 China.

^# Contributed equally.

Abstract

Background: 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. 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.

Results: 1,25(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.

Conclusion: Deficiency 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.

Keywords: 1,25(OH)2D3 deficiency; Colonic mucus barrier; Gut microbiota; Inflammatory bowel disease.