Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice
Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice
复制标题
肠道菌群失调会加重患者和小鼠急性胰腺炎的严重程度
DOI:
10.1007/s00535-018-1529-0
复制
发表时间:
2019-04-01
影响因子:
6.3
通讯作者:
Lu, Nonghua
中科院分区:
文献类型:
--
作者:
Zhu, Yin;He, Cong;Lu, Nonghua
BackgroundThe gut is implicated in the pathogenesis of acute pancreatitis (AP) and the infectious complications of AP are commonly associated with enteric bacteria, yet whether gut microbiota dysbiosis participants in AP severity remains largely unknown.MethodsWe collected clinical information and fecal samples from 165 adult participants, including 41 with mild AP (MAP), 59 with moderately severe AP (MSAP), 30 with severe AP (SAP) and 35 healthy controls (HC). The serum inflammatory cytokines and gut barrier indexes were detected. Male C57BL/6 mice with AP were established and injuries of pancreas were evaluated in antibiotic-treated mice, germ-free mice as well as those transplanted with fecal microbiota. The gut microbiota was analyzed by 16S rRNA gene sequencing.ResultsThe structure of gut microbiota was significantly different between AP and HC, and the disturbed microbiota was closely correlated with systematic inflammation and gut barrier dysfunction. Notably, the microbial composition changed further with the worsening of AP and the abundance of beneficial bacteria such asBlautiawas decreased in SAP compared with MAP and MSAP. The increased capacity for the inferred pathway, bacterial invasion of epithelial cells in AP, highly correlated with the abundance ofEscherichia–Shigella. Furthermore, the antibiotic-treated mice and germ-free mice exhibited alleviated pancreatic injury after AP induction and subsequent fecal microbiota transplantation in turn exacerbated the disease.ConclusionsThis study identifies the gut microbiota as an important mediator during AP and its dysbiosis is associated with AP severity, which suggests its role as potential therapeutic target.