Commensal <i>Escherichia coli</i> Aggravates Acute Necrotizing Pancreatitis through Targeting of Intestinal Epithelial Cells

Abstract

An increase of <i>Escherichia-Shigella</i> was previously reported in acute necrotizing pancreatitis (ANP). We investigated whether <i>Escherichia coli</i> MG1655, an <i>Escherichia</i> 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 <i>E. coli</i> MG1655 in ANP. Afterward, administration of <i>E. coli</i> MG1655 by gavage to gut microbiota-depleted rats with ANP was performed. We observed that after ANP induction, <i>E. coli</i> 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. <i>In vitro</i>, 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 <i>E. coli</i> MG1655, as well as TLR4, MyD88, and Bip upregulation. In conclusion, our study shows that commensal <i>E. coli</i> 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 <i>E. coli</i> in ANP.<b>IMPORTANCE</b> This study describes the harmful potential of commensal <i>E. coli</i> 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.