Yin Zhu1, Cong He1, Xueyang Li1, Yan Cai1, Jinxiang Hu2, Yuanhang Liao1, Jianhua Zhao2, Liang Xia1, Wenhua He1, Linmeng Liu2, Chun Luo2, Xu Shu1, Qiang Cai3, Youxiang Chen1, Nonghua Lu4. 1. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yong Waizheng Street, Donghu District, Nanchang, 330006, Jiangxi, China. 2. Shanghai Major Bio-pharm Technology Co., Ltd, Shanghai, 201203, China. 3. Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. 4. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yong Waizheng Street, Donghu District, Nanchang, 330006, Jiangxi, China. lunonghua@ncu.edu.cn.
Abstract
BACKGROUND: The 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. METHODS: We 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. RESULTS: The 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 as Blautia was 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 of Escherichia-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. CONCLUSIONS: This 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.
BACKGROUND: The 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 dysbiosisparticipants in AP severity remains largely unknown. METHODS: We 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. RESULTS: The 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 as Blautia was 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 of Escherichia-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. CONCLUSIONS: This 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.
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