Cocaine Induces Inflammatory Gut Milieu by Compromising the Mucosal Barrier Integrity and Altering the Gut Microbiota Colonization
Cocaine Induces Inflammatory Gut Milieu by Compromising the Mucosal Barrier Integrity and Altering the Gut Microbiota Colonization
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DOI：
10.1038/s41598-019-48428-2
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发表时间：
2019-08-21
影响因子：
4.6
通讯作者：
Buch, Shilpa
中科院分区：
文献类型：
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作者：
Chivero, Ernest T.;Ahmad, Rizwan;Buch, Shilpa
可卡因使用障碍（CUD）是一种主要的健康危机，传统上被认为是中枢神经系统的并发症；然而，它也与营养不良和肠道健康恶化密切相关。鉴于肠道微生物群在神经系统疾病中的潜在作用的新兴研究，我们试图了解CUD和肠道生态失调之间的因果关系。采用综合方法，我们证实小鼠服用可卡因会导致肠道微生物群的改变。此外，可卡因介导的肠道生态失调与促炎介质（包括nf - κ B和IL-1 β）的上调有关。体内和体外分析证实，可卡因改变了肠屏障紧密连接蛋白的组成，同时也通过可能涉及MAPK/ERK1/2信号通路损害上皮通透性。综上所述，我们的研究结果揭示了CUD、肠道屏障功能障碍和生态失调之间的因果关系，并为未来开发处理cudd相关肠道并发症的补充策略奠定了基础。
Cocaine use disorder (CUD), a major health crisis, has traditionally been considered a complication of the CNS; however, it is also closely associated with malnourishment and deteriorating gut health. In light of emerging studies on the potential role of gut microbiota in neurological disorders, we sought to understand the causal association between CUD and gut dysbiosis. Using a comprehensive approach, we confirmed that cocaine administration in mice resulted in alterations of the gut microbiota. Furthermore, cocaine-mediated gut dysbiosis was associated with upregulation of proinflammatory mediators including NF-kappa B and IL-1 beta. In vivo and in vitro analyses confirmed that cocaine altered gut-barrier composition of the tight junction proteins while also impairing epithelial permeability by potentially involving the MAPK/ERK1/2 signaling. Taken together, our findings unravel a causal link between CUD, gut-barrier dysfunction and dysbiosis and set a stage for future development of supplemental strategies for the management of CUD-associated gut complications.