1,25(OH)(2)D(3) deficiency-induced gut microbial dysbiosis degrades the colonic mucus barrier in Cyp27b1 knockout mouse model

BACKGROUND: The relationship between disturbances of the gut microbiota and 1,25(OH)(2)D(3) 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)(2)D(3) had significant colon inflammation phenotypes. However, whether and how 1,25(OH)(2)D(3) 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)(2)D(3) 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)(2)D(3) 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)(2)D(3) supplement significantly decreased Akkermansia muciniphila abundance in fecal samples of Cyp27b1(−/−) mice. CONCLUSION: Deficiency in 1,25(OH)(2)D(3) 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)(2)D(3) status, the gut microbiota and the colonic mucus barrier that is regarded as a primary defense against enteric pathogens.