Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice.
Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice.
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微生物群通过调节小鼠宿主基因表达来防止体内胆固醇流失
DOI：
10.1038/srep10512
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发表时间：
2015-05-27
影响因子：
4.6
通讯作者：
Song ZY
中科院分区：
文献类型：
--
作者：
Zhong CY;Sun WW;Ma Y;Zhu H;Yang P;Wei H;Zeng BH;Zhang Q;Liu Y;Li WX;Chen Y;Yu L;Song ZY
我们先前观察到，敲除Niemann-Pick C1-like 1(NPC1L1)，一种对肠道胆固醇吸收至关重要的胆固醇转运体，会减少小鼠干粪便的排出量。由于NPC1L1基因敲除(L1-KO)小鼠的摄食量没有改变，我们假设NPC1L1缺乏可能会改变肠道微生物群，从而减少粪便产量。始终如一地，我们在这里证明了L1-KO小鼠和它们的野生型对照动物之间的粪便微生物区系有很大的不同。无菌(GF)小鼠的粪便排出量减少。用其抑制剂ezetimibe抑制NPC1L1可以减少无特定病原体(SPF)小鼠的粪便产量，但不会减少GF小鼠的粪便产量。此外，我们发现，与SPF小鼠相比，GF小鼠的肠道吸收减少，粪便胆固醇排泄增加，特别是在使用依折麦布治疗后。在GF小鼠中，胆固醇的负平衡与血浆和肝脏胆固醇的降低有关，可能是由于NPC1L1的表达减少以及小肠中ABCG5和ABCG8的表达增加所致。肠道和肝脏中其他基因的表达水平在很大程度上反映了胆固醇耗竭的状态和肠道对胆汁酸的感觉下降。总之，我们的发现揭示了微生物区系在调节全身胆固醇稳态及其对降胆固醇药物依折麦布的反应方面的广泛作用。
We have previously observed that knockout of Niemann-Pick C1-Like 1 (NPC1L1), a cholesterol transporter essential for intestinal cholesterol absorption, reduces the output of dry stool in mice. As the food intake remains unaltered in NPC1L1-knockout (L1-KO) mice, we hypothesized that NPC1L1 deficiency may alter the gut microbiome to reduce stool output. Consistently, here we demonstrate that the phyla of fecal microbiota differ substantially between L1-KO mice and their wild-type controls. Germ-free (GF) mice have reduced stool output. Inhibition of NPC1L1 by its inhibitor ezetimibe reduces stool output in specific pathogen-free (SPF), but not GF mice. In addition, we show that GF versus SPF mice have reduced intestinal absorption and increased fecal excretion of cholesterol, particularly after treatment with ezetimibe. This negative balance of cholesterol in GF mice is associated with reduced plasma and hepatic cholesterol and likely caused by reduced expression of NPC1L1 and increased expression of ABCG5 and ABCG8 in small intestine. Expression levels of other genes in intestine and liver largely reflect a state of cholesterol depletion and a decrease in intestinal sensing of bile acids. Altogether, our findings reveal a broad role of microbiota in regulating whole-body cholesterol homeostasis and its response to a cholesterol-lowering drug, ezetimibe.
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影响因子：
6.5
作者：
Freeman, LA;Kennedy, A;Brewer, HB
通讯作者：
Brewer, HB
影响因子：
15.9
作者：
Graf, GA;Li, WP;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
56.9
作者：
Altmann, SW;Davis, HR;Graziano, MP
通讯作者：
Graziano, MP
DOI：
10.1073/pnas.1534923100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Horton, JD;Shah, NA;Goldstein, JL
通讯作者：
Goldstein, JL
影响因子：
6.5
作者：
Jia, Lin;Ma, Yinyan;Yu, Liqing
通讯作者：
Yu, Liqing