The Intestinal Effect of Atorvastatin: Akkermansia muciniphila and Barrier Function.
The Intestinal Effect of Atorvastatin: Akkermansia muciniphila and Barrier Function.
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阿托伐他汀的肠道作用：Akkermansia muciniphila 和屏障功能
DOI：
10.3389/fmicb.2021.797062
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发表时间：
2021
影响因子：
5.2
通讯作者：
Feng B
中科院分区：
文献类型：
--
作者：
Cheng T;Li C;Shen L;Wang S;Li X;Fu C;Li T;Liu B;Gu Y;Wang W;Feng B
研究表明，降胆固醇药物他汀类药物改变肠道微生物组，诱导慢性代谢性炎症，并破坏血糖稳态。在这项研究中，我们旨在研究阿托伐他汀（Ator）对肠道微生物组和代谢性炎症的影响是否存在因果关系。8周龄的小鼠用高脂饮食（HFD）或HFD + Ator（HFD + Ator）喂养16周。粪便16S rRNA测序和结肠组织RNA测序分析Ator可能引起的肠道变化。人结肠癌细胞系（Caco 2）用于屏障功能的体外实验。与HFD相比，HFD + Ator诱导更多的体重增加，葡萄糖耐量受损，并导致肠道微生物群生态失调，例如抑制小鼠中的嗜粘蛋白阿克曼氏菌。HFD + Ator小鼠结肠紧密连接（TJ）蛋白表达减弱，血清脂多糖结合蛋白（LBP）水平升高，从而转录激活了肠核因子-κ基因结合（NF-κ B）信号通路。结论Ator对Caco 2屏障功能有明显的损伤作用，而对A.嗜粘蛋白培养物可降低肠通透性，恢复Ator诱导的TJ蛋白表达减弱。总之，长期使用Ator与HFD可能会改变肠道菌群，诱导肠道屏障功能障碍，从而促进慢性炎症，导致血糖稳态破坏。
Studies have shown that the cholesterol-lowering medicine statins alter the gut microbiome, induce chronic metabolic inflammation, and disrupt glycemic homeostasis. In this study, we aimed to investigate whether effects of atorvastatin (Ator) on gut microbiome and metabolic inflammation could be causally correlated. Mice at 8-week age were fed with high-fat diet (HFD) or HFD with Ator (HFD+Ator) for 16 weeks. 16S rRNA sequencing of stool and RNA sequencing of colon tissue were employed to analyze the intestinal alterations that could be induced by Ator. A human colon carcinoma cell line (Caco2) was used for in vitro experiments on barrier function. Compared to HFD, HFD+Ator induced more weight gain, impaired glucose tolerance, and led to gut microbiota dysbiosis, such as suppressing Akkermansia muciniphila in mice. The expressions of tight junction (TJ) proteins were attenuated in the colon, and the serum LPS-binding-protein (LBP) level was elevated in HFD+Ator mice, so as to transcriptionally activate the intestinal nuclear factor-k-gene binding (NF-κB) signaling pathway. Consistently, Ator impaired the barrier function of Caco2, and treatment of supernatant of A. Muciniphila culture could decrease the intestinal permeability and recover the attenuated expression of TJ proteins induced by Ator. In conclusion, long-term use of Ator with HFD may alter gut microbiota, induce intestinal barrier dysfunction, and hence promote chronic inflammation that contributes to disrupted glycemic homeostasis.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
12.8
作者：
Chelakkot C;Choi Y;Kim DK;Park HT;Ghim J;Kwon Y;Jeon J;Kim MS;Jee YK;Gho YS;Park HS;Kim YK;Ryu SH
通讯作者：
Ryu SH
影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
82.9
作者：
Depommier, Clara;Everard, Amandine;Cani, Patrice D.
通讯作者：
Cani, Patrice D.
影响因子：
9.3
作者：
Almeida, Shone O.;Budoff, Matthew
通讯作者：
Budoff, Matthew