Antibiotic-Induced Pathobiont Dissemination Accelerates Mortality in Severe Experimental Pancreatitis.
Antibiotic-Induced Pathobiont Dissemination Accelerates Mortality in Severe Experimental Pancreatitis.
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DOI：
10.3389/fimmu.2017.01890
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发表时间：
2017
影响因子：
7.3
通讯作者：
Spiller F
中科院分区：
文献类型：
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作者：
Soares FS;Amaral FC;Silva NLC;Valente MR;Santos LKR;Yamashiro LH;Scheffer MC;Castanheira FVES;Ferreira RG;Gehrke L;Alves-Filho JC;Silva LP;Báfica A;Spiller F
虽然抗生素引起的生态失调已被证明会加剧肠道炎症，但已有研究表明，抗生素预防可能对某些临床疾病（如急性胰腺炎（AP））有益。然而，广谱抗生素，如美罗培南，是否会影响严重AP期间多药耐药（MDR）细菌的传播尚未得到解决。本研究采用梗阻性重度AP小鼠模型，探讨美罗培南预处理对细菌传播和疾病结局的影响。正如预期的那样，胆胰管阻塞的动物发生了严重的AP。令人惊讶的是，与盐水预处理的AP小鼠（中位生存期为7天）相比，美罗培南预处理的AP小鼠的死亡率（中位生存期为2天）加快了。早期死亡与耐多药菌株易位有关，主要是鸡肠球菌进入血流。在富含鸡大肠杆菌的小鼠肠道中诱导AP，再现了在美罗培宁预处理的AP小鼠中观察到的死亡率增加。此外，naïve小鼠受到小鼠或鸡大肠杆菌临床菌株的攻击，通过toll样受体-2的机制死于感染。这些结果证实，广谱抗生素可能在炎症性疾病期间导致间接有害影响，并揭示了一种与小鼠阻塞性AP期间美罗培南预处理相关的肠道病原体。
Although antibiotic-induced dysbiosis has been demonstrated to exacerbate intestinal inflammation, it has been suggested that antibiotic prophylaxis may be beneficial in certain clinical conditions such as acute pancreatitis (AP). However, whether broad-spectrum antibiotics, such as meropenem, influence the dissemination of multidrug-resistant (MDR) bacteria during severe AP has not been addressed. In the currently study, a mouse model of obstructive severe AP was employed to investigate the effects of pretreatment with meropenem on bacteria spreading and disease outcome. As expected, animals subjected to biliopancreatic duct obstruction developed severe AP. Surprisingly, pretreatment with meropenem accelerated the mortality of AP mice (survival median of 2 days) when compared to saline-pretreated AP mice (survival median of 7 days). Early mortality was associated with the translocation of MDR strains, mainly Enterococcus gallinarum into the blood stream. Induction of AP in mice with guts that were enriched with E. gallinarum recapitulated the increased mortality rate observed in the meropenem-pretreated AP mice. Furthermore, naïve mice challenged with a mouse or a clinical strain of E. gallinarum succumbed to infection through a mechanism involving toll-like receptor-2. These results confirm that broad-spectrum antibiotics may lead to indirect detrimental effects during inflammatory disease and reveal an intestinal pathobiont that is associated with the meropenem pretreatment during obstructive AP in mice.
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影响因子：
64.8
作者：
Brandl, Katharina;Plitas, George;Mihu, Coralia N.;Ubeda, Carles;Jia, Ting;Fleisher, Martin;Schnabl, Bernd;DeMatteo, Ronald P.;Pamer, Eric G.
通讯作者：
Pamer, Eric G.
影响因子：
3.7
作者：
Abayasekara LM;Perera J;Chandrasekharan V;Gnanam VS;Udunuwara NA;Liyanage DS;Bulathsinhala NE;Adikary S;Aluthmuhandiram JVS;Thanaseelan CS;Tharmakulasingam DP;Karunakaran T;Ilango J
通讯作者：
Ilango J
影响因子：
28.3
作者：
Gibson, Molly K.;Wang, Bin;Ahmadi, Sara;Burnham, Carey-Ann D.;Tarr, Phillip I.;Warner, Barbara B.;Dantas, Gautam
通讯作者：
Dantas, Gautam
影响因子：
24.5
作者：
Knoop KA;McDonald KG;Kulkarni DH;Newberry RD
通讯作者：
Newberry RD
影响因子：
82.9
作者：
通讯作者：
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