Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice
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.
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.
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.
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.
KeywordsAcute pancreatitis Gut microbiota Intestinal barrier Antibiotic treatment Fecal microbiota transplantation
The authors are grateful for all the subjects who participated in this study. The authors acknowledge Dr. Jianping Liu in Karolinska Institute, Sweden for revising the manuscript.
NL and YC designed and supervised the project. YZ obtained funding. YZ, LX, WH and XS performed clinical diagnosis and selected proper cases for this project. YL collected the fecal samples and recorded clinical data. YL, YC and CH measured the clinical parameters. YC and XL performed the animal experiments. CH, JH, JZ, LL and CL performed bioinformatics and statistical analysis and interpreted data. CH drafted the manuscript. YZ and QC revised the manuscript for important content.
This work was supported by grants from the National Natural Science Foundation of China (81760120, 81460116), the Key Research and Development Program from the Science and Technology Department of Jiangxi Province (no. 20171BBG70084).
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Conflict of interest
The authors declare that they have no competing interests.
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