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肠道微生物群加剧了高脂血症性胰腺炎中中性粒细胞胞外诱捕网诱导的胰腺损伤。

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

机构信息

Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.

Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, 150001, China.

出版信息

Nat Commun. 2023 Oct 4;14(1):6179. doi: 10.1038/s41467-023-41950-y.


DOI:10.1038/s41467-023-41950-y
PMID:37794047
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10550972/
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.

摘要

高脂血症性胰腺炎 (HTGP) 的特点是并发症发生率更高,临床结局较差。肠道微生物失调与 HTGP 中的胰腺损伤有关,但具体机制尚不清楚。在这里,我们观察到 HTGP 患者的肠道微生物多样性较低,有益细菌缺失。在粪便微生物移植小鼠模型中,HTGP 患者的肠道菌群定植会招募中性粒细胞并增加中性粒细胞胞外陷阱 (NETs) 的形成,从而加重胰腺损伤和全身炎症。我们发现肠道微生物群中均匀拟杆菌的丰度降低会损害牛磺酸的产生并增加结肠中 IL-17 的释放,从而触发 NETs 的形成。此外,均匀拟杆菌或牛磺酸可抑制中性粒细胞中 NF-κB 和 IL-17 信号通路的激活,从而利用 NETs 并减轻胰腺损伤。我们的研究结果确立了内源性均匀拟杆菌衍生的代谢和炎症产物在抑制 NETs 释放中的作用,这为通过肠道微生物群调节改善 HTGP 提供了潜在的见解。

相似文献

[1]
Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis.

Nat Commun. 2023-10-4

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Biomarkers to predict the severity of acute pancreatitis.

Front Med (Lausanne). 2025-8-6

[2]
Related differences in fecal bacteria of Chinese northern pregnant women of different ages: associations with maternal clinical indicators and neonatal outcomes.

Front Microbiol. 2025-7-18

[3]
Hypertriglyceridemic pancreatitis: perspectives from China.

Curr Opin Gastroenterol. 2025-9-1

[4]
Gut microbiota from voluntary exercised mice protects the intestinal barrier by inhibiting neutrophil extracellular trap formation.

iScience. 2025-5-27

[5]
Neutrophil extracellular traps in cancer: From mechanisms to treatments.

Clin Transl Med. 2025-6

[6]
Identification of Grb2 protein as a potential mediator of macrophage activation in acute pancreatitis based on bioinformatics and experimental verification.

Front Immunol. 2025-5-26

[7]
Dynamic relationship between gut microbiota and post-necrotizing pancreatitis: insights from a multi-stage 16S rRNA sequencing study.

Front Pharmacol. 2025-5-22

[8]
Akkermansia Muciniphila Alleviates Severe Acute Pancreatitis via Amuc1409-Ube2k-Foxp3 Axis in Regulatory T Cells.

Adv Sci (Weinh). 2025-8

[9]
Gut microbiota deficiency reduces neutrophil activation and is protective after ischemic stroke.

J Neuroinflammation. 2025-5-23

[10]
promotes gallstone formation by inducing intrahepatic neutrophil extracellular traps through CXCL1 produced by colonic epithelial cells.

Microb Cell. 2025-3-19

本文引用的文献

[1]
Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer.

Nat Microbiol. 2023-5

[2]
Activated regulatory T-cells promote duodenal bacterial translocation into necrotic areas in severe acute pancreatitis.

Gut. 2023-7

[3]
Gut microbiota-derived nicotinamide mononucleotide alleviates acute pancreatitis by activating pancreatic SIRT3 signalling.

Br J Pharmacol. 2023-3

[4]
Gut microbiome dysbiosis contributes to abdominal aortic aneurysm by promoting neutrophil extracellular trap formation.

Cell Host Microbe. 2022-10-12

[5]
spp. and their metabolite lactate protect against acute pancreatitis via inhibition of pancreatic and systemic inflammatory responses.

Gut Microbes. 2022

[6]
Taurine inhibits induced NADPH oxidase-dependent neutrophil extracellular traps TAK1/MAPK signaling pathways.

Front Immunol. 2022

[7]
Intestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency.

Gut Microbes. 2022

[8]
Mechanism of taurine reducing inflammation and organ injury in sepsis mice.

Cell Immunol. 2022-5

[9]
Human gut bacteria produce Τ17-modulating bile acid metabolites.

Nature. 2022-3

[10]
Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications.

Nat Commun. 2022-2-23

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