Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis

Guanqun Li, Liwei Liu, Tianqi Lu, Yuhang Sui, Can Zhang, Yongwei Wang, Tao Zhang, Yu Xie, Peng Xiao, Zhongjie Zhao, Chundong Cheng, Jisheng Hu, Hongze Chen, Dongbo Xue, Hua Chen, Gang Wang, Rui Kong, Hongtao Tan, Xuewei Bai, Zhibo Li, Florencia McAllister, Le Li () and Bei Sun ()
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Guanqun Li: The First Affiliated Hospital of Harbin Medical University
Liwei Liu: The First Affiliated Hospital of Harbin Medical University
Tianqi Lu: The First Affiliated Hospital of Harbin Medical University
Yuhang Sui: The First Affiliated Hospital of Harbin Medical University
Can Zhang: The First Affiliated Hospital of Harbin Medical University
Yongwei Wang: The First Affiliated Hospital of Harbin Medical University
Tao Zhang: The First Affiliated Hospital of Harbin Medical University
Yu Xie: The First Affiliated Hospital of Harbin Medical University
Peng Xiao: The First Affiliated Hospital of Harbin Medical University
Zhongjie Zhao: The First Affiliated Hospital of Harbin Medical University
Chundong Cheng: The First Affiliated Hospital of Harbin Medical University
Jisheng Hu: The First Affiliated Hospital of Harbin Medical University
Hongze Chen: The First Affiliated Hospital of Harbin Medical University
Dongbo Xue: The First Affiliated Hospital of Harbin Medical University
Hua Chen: The First Affiliated Hospital of Harbin Medical University
Gang Wang: The First Affiliated Hospital of Harbin Medical University
Rui Kong: The First Affiliated Hospital of Harbin Medical University
Hongtao Tan: The First Affiliated Hospital of Harbin Medical University
Xuewei Bai: The First Affiliated Hospital of Harbin Medical University
Zhibo Li: The First Affiliated Hospital of Harbin Medical University
Florencia McAllister: The University of Texas MD Anderson Cancer Center
Le Li: The First Affiliated Hospital of Harbin Medical University
Bei Sun: The First Affiliated Hospital of Harbin Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. Moreover, Bacteroides uniformis or taurine inhibits the activation of NF-κB and IL-17 signaling pathways in neutrophils which harness NETs and alleviate pancreatic injury. Our findings establish roles of endogenous Bacteroides uniformis-derived metabolic and inflammatory products on suppressing NETs release, which provides potential insights of ameliorating HTGP through gut microbiota modulation.

Date: 2023
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DOI: 10.1038/s41467-023-41950-y

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