1,25(OH)2D3 deficiency‑induced gut microbial dysbiosis degrades the colonic mucus barrier in Cyp27b1 knockout mouse model
1,25(OH)2D3 deficiency‑induced gut microbial dysbiosis degrades the colonic mucus barrier in Cyp27b1 knockout mouse model
复制标题
Cyp27b1 敲除小鼠模型中 1,25(OH)2D3 缺乏引起的肠道微生物失调会降低结肠粘液屏障
DOI：
10.1186/s13099-019-0291-z
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发表时间：
2019
期刊：
影响因子：
4.2
通讯作者：
Xiaoqin Yuan
中科院分区：
文献类型：
--
作者：
Wenjing Zhu;Jiayao Yan;Chunchun Zhi;Qianwen Zhou;Xiaoqin Yuan
背景：肠道微生物群失调和1，25（OH）2D 3缺乏之间的关系已经在人类和维生素D缺乏饮食或缺乏阳光照射的动物模型中得到证实。我们先前的研究已经证明，Cyp 27 b1-/-（Cyp 27 b1敲除）小鼠不能产生1，25（OH）2D 3，具有显著的结肠炎症表型。然而，由于基因缺失导致的1，25（OH）2D 3缺乏是否以及如何控制肠道内稳态并调节肠道微生物群的组成仍有待探索。结果：1，25（OH）2D 3缺乏会损害Cyp 27 b1-/-小鼠肠道微生物群和代谢产物的组成，包括嗜粘蛋白阿克曼氏菌、加拿大孤蚁、产酸拟杆菌、普通拟杆菌和SCFA的产生。1，25（OH）2D 3缺乏导致结肠粘液层变薄并增加细菌向肠系膜淋巴结的移位。我们还发现1，25（OH）2D 3补充剂显著降低Cyp 27 b1-/-小鼠粪便样品中嗜粘蛋白阿克曼氏菌的丰度。结论：1，25（OH）2D 3缺乏会损害肠道菌群的组成，导致肠上皮屏障稳态的破坏和结肠炎症的诱导。这项研究强调了1，25（OH）2D 3状态，肠道微生物群和结肠粘液屏障之间的关联，结肠粘液屏障被认为是对抗肠道病原体的主要防御。
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.