Commensal Escherichia coli Aggravates Acute Necrotizing Pancreatitis through Targeting of Intestinal Epithelial Cells
Commensal Escherichia coli Aggravates Acute Necrotizing Pancreatitis through Targeting of Intestinal Epithelial Cells
复制标题
共生大肠杆菌通过靶向肠上皮细胞加重急性坏死性胰腺炎
DOI：
10.1128/aem.00059-19
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发表时间：
2019-06-01
影响因子：
4.4
通讯作者：
Zeng, Yue
中科院分区：
文献类型：
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作者：
Zheng, Junyuan;Lou, Lihong;Zeng, Yue
这项研究描述了共生大肠杆菌在ANP中的有害潜力，这在以前的研究中还没有得到证实。我们的工作为肠道细菌-ANP交叉对话提供了新的见解，表明非致病共生菌也可能在疾病背景下表现出不利影响。摘要急性坏死性胰腺炎(ANP)患者的肠出血性志贺氏菌增多。我们研究了大肠杆菌MG1655是否增加了大鼠的肠道损伤和加重了ANP。逆行胆胰管注射3.5%牛磺胆酸钠诱导ANP。利用肠道微生物区系耗竭的大鼠，我们证明肠道微生物区系参与了ANP的胰腺损伤和肠屏障功能障碍。通过16S rRNA基因测序和定量聚合酶链式反应，我们发现肠道菌群失调，ANP中的E.ColiMG1655菌株显著增加。随后，对肠道微生物区系耗竭的ANP大鼠进行了灌胃给药。我们观察到，在ANP诱导后，大肠杆菌MG1655单克隆大鼠的胰腺和肠道屏障功能的损伤比肠道微生物区系枯竭的大鼠更严重。此外，MG1655单克隆ANP大鼠肠上皮细胞Toll样受体4(TLR4)/MyD88/p38丝裂原激活蛋白(MAPK)和内质网应激(ERS)活性也显著增加。在体外，大鼠回肠上皮细胞株IEC-18在与大肠杆菌MG1655共同培养时，表现出肿瘤坏死因子α诱导的炎症和紧密连接蛋白的丢失，以及TLR4、MyD88和Bip的上调。综上所述，我们的研究表明，共生大肠杆菌MG1655增加了TLR4/MyD88/p38 MAPK和ERS信号诱导的大鼠肠上皮损伤，加重了ANP。我们的研究还描述了共生大肠杆菌在ANP中的有害潜力。重要性这项研究描述了共生大肠杆菌在ANP中的有害潜力，这在以前的研究中还没有得到证实。我们的工作为肠道细菌-ANP交叉对话提供了新的见解，表明非致病共生菌也可能在疾病背景下表现出不利影响。
This study describes the harmful potential of commensal E. coli in ANP, which has not been demonstrated in previous studies. Our work provides new insights into gut bacterium-ANP cross talk, suggesting that nonpathogenic commensals could also exhibit adverse effects in the context of diseases. ABSTRACT An increase of Escherichia-Shigella was previously reported in acute necrotizing pancreatitis (ANP). We investigated whether Escherichia coli MG1655, an Escherichia commensal organism, increased intestinal injury and aggravated ANP in rats. ANP was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct. Using gut microbiota-depleted rats, we demonstrated that gut microbiota was involved in the pancreatic injury and intestinal barrier dysfunction in ANP. Using 16S rRNA gene sequencing and quantitative PCR, we found intestinal dysbiosis and a significant increase of E. coli MG1655 in ANP. Afterward, administration of E. coli MG1655 by gavage to gut microbiota-depleted rats with ANP was performed. We observed that after ANP induction, E. coli MG1655-monocolonized rats presented more severe injury in the pancreas and intestinal barrier function than gut microbiota-depleted rats. Furthermore, Toll-like receptor 4 (TLR4)/MyD88/p38 mitogen-activated protein (MAPK) and endoplasmic reticulum stress (ERS) activation in intestinal epithelial cells were also increased more significantly in the MG1655-monocolonized ANP rats. In vitro, the rat ileal epithelial cell line IEC-18 displayed aggravated tumor necrosis factor alpha-induced inflammation and loss of tight-junction proteins in coculture with E. coli MG1655, as well as TLR4, MyD88, and Bip upregulation. In conclusion, our study shows that commensal E. coli MG1655 increases TLR4/MyD88/p38 MAPK and ERS signaling-induced intestinal epithelial injury and aggravates ANP in rats. Our study also describes the harmful potential of commensal E. coli in ANP. IMPORTANCE This study describes the harmful potential of commensal E. coli in ANP, which has not been demonstrated in previous studies. Our work provides new insights into gut bacterium-ANP cross talk, suggesting that nonpathogenic commensals could also exhibit adverse effects in the context of diseases.