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Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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.

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Acknowledgements

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.

Funding

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).

Author information

Author notes

  1. Yin Zhu, Cong He and Xueyang Li joint first coauthorship.

  2. Youxiang Chen and Nonghua Lu joint last coauthorship.

Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yong Waizheng Street, Donghu District, Nanchang, 330006, Jiangxi, China

    Yin Zhu, Cong He, Xueyang Li, Yan Cai, Yuanhang Liao, Liang Xia, Wenhua He, Xu Shu, Youxiang Chen & Nonghua Lu

  2. Shanghai Major Bio-pharm Technology Co., Ltd, Shanghai, 201203, China

    Jinxiang Hu, Jianhua Zhao, Linmeng Liu & Chun Luo

  3. Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Qiang Cai

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  1. Yin Zhu
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  2. Cong He
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Contributions

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.

Corresponding author

Correspondence to Nonghua Lu.

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The authors declare that they have no competing interests.

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Cite this article

Zhu, Y., He, C., Li, X. et al. Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice. J Gastroenterol 54, 347–358 (2019). https://doi.org/10.1007/s00535-018-1529-0

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  • DOI: https://doi.org/10.1007/s00535-018-1529-0

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