Gentamicin Induced Microbiome Adaptations Associate With Increased BCAA Levels and Enhance Severity of Influenza Infection.
Gentamicin Induced Microbiome Adaptations Associate With Increased BCAA Levels and Enhance Severity of Influenza Infection.
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庆大霉素诱导的微生物组适应与 BCAA 水平升高和流感感染严重程度增加相关
DOI：
10.3389/fimmu.2020.608895
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发表时间：
2020
影响因子：
7.3
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Sun Y;He Z;Li J;Gong S;Yuan S;Li T;Ning N;Xing L;Zhang L;Chen F;Li Z;Wang J;Luo D;Wang H
已经广泛观察到肠道微生物群通过肠-肺轴参与肺部疾病。然而，呼吸道粘膜免疫和肠道微生物群之间的串扰信使在很大程度上是未知的。使用肠道微环境小鼠模型的选择性药理学破坏，我们发现庆大霉素处理的小鼠中肠道微生物群显示出显著较低的α多样性和细菌的相对丰度。宏基因组研究揭示了肠道细菌在改变小鼠血液代谢谱方面的功能差异。支链氨基酸（BCAA）是连接肠和肺的重要因素。在此过程中，庆大霉素对肠道微生物群的选择性破坏诱导了高水平的BCAA，而高水平的BCAA影响了肺对流感病毒的免疫力。在体内，庆大霉素处理的小鼠或喂食高支链氨基酸饮食的小鼠显示存活率降低。在感染部位，CD 11b + Ly 6 G+细胞减少，CD 8 + T细胞增多，并伴有促炎细胞因子的过度表达，可导致组织损伤。CD 11b + Ly 6 G+细胞移植对流感病毒感染具有显著的保护作用。在体外，支链氨基酸促进骨髓来源的细胞分化为树突状细胞。综上所述，这些发现表明，庆大霉素诱导的肠道微生物群破坏导致BCAA水平增加，从而抑制与过度活跃的CD 8 + T反应相关的CD 11b + Ly 6c+细胞发育，这可能导致病毒感染的严重程度增加。
Involvement of gut microbiota in pulmonary disease by the gut-lung axis has been widely observed. However, the cross-talk messengers between respiratory mucosal immunity and gut microbiota are largely unknown. Using selective pharmacologic destruction of gut microenvironment mouse models, we found gut microbiota displayed significantly lower alpha diversity and relative abundance of bacteria in Gentamicin treated mice. Metagenomic studies revealed functional differences in gut bacteria in altering metabolic profiles in mice blood. Branched-chain amino acids (BCAAs) are the essential factors linked between gut and lung. During this process, selective destruction of gut microbiota by Gentamicin induced high levels of BCAAs, and the high levels of BCAAs impacted the lung immunity against influenza virus. In vivo, Gentamicin-treated mice or mice fed with high BCAAs diets displayed reduced survival. At the sites of infection, the number of CD11b+Ly6G+ cells decreased, and CD8+ T cells increased accompanied by exuberant expression of pro-inflammatory cytokines could result in tissue damage. CD11b+Ly6G+ cells transplantation conferred remarkable protection from influenza virus infections. In vitro, BCAAs promoted bone marrow-derived cells differentiation to dendritic cells. Taken together, these findings demonstrate that Gentamicin induced disruption of the gut microbiota leads to increased BCAA levels that suppress CD11b+Ly6c+ cell development in association with overactive CD8+ T responses which may contribute to enhanced severity of the viral infection.
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影响因子：
64.8
作者：
Finisguerra V;Di Conza G;Di Matteo M;Serneels J;Costa S;Thompson AA;Wauters E;Walmsley S;Prenen H;Granot Z;Casazza A;Mazzone M
通讯作者：
Mazzone M
影响因子：
20.3
作者：
Movahedi, Kiavash;Guilliams, Martin;Van Ginderachter, Jo A.
通讯作者：
Van Ginderachter, Jo A.
DOI：
10.1073/pnas.1019378108
发表时间：
2011-03-29
影响因子：
11.1
作者：
Ichinohe, Takeshi;Pang, Iris K.;Iwasaki, Akiko
通讯作者：
Iwasaki, Akiko
新生儿中骨髓源性抑制细胞的短暂存在对于控制炎症至关重要。
影响因子：
82.9
作者：
He YM;Li X;Perego M;Nefedova Y;Kossenkov AV;Jensen EA;Kagan V;Liu YF;Fu SY;Ye QJ;Zhou YH;Wei L;Gabrilovich DI;Zhou J
通讯作者：
Zhou J
影响因子：
2.7
作者：
Lagkouvardos, Ilias;Fischer, Sandra;Clavel, Thomas
通讯作者：
Clavel, Thomas