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