Department of Gastroenterology, The First Affiliated Hospital of Nanchang University , Nanchang, Jiangxi, China.
Gut Microbes. 2020 Nov 1;11(6):1774-1789. doi: 10.1080/19490976.2020.1770042. Epub 2020 Jun 12.
Early dysbiosis of the gut microbiota is associated with the severity of acute pancreatitis (AP), although the underlying mechanism is unclear. Here, we investigated the role of crosstalk between NLRP3 and the gut microbiota in the development of AP utilizing gut microbiota deficient mice, as well as NLRP3 knockout (KO) mouse models. Pancreatic damage and systemic inflammation were improved in antibiotic-treated (Abx) and germ-free (GF) mice, accompanied by weakened activity of the intestinal NLRP3 inflammasome. Interestingly, fecal microbiota transplantation (FMT) reactivated the intestinal NLRP3 inflammasome and exacerbated the disease in Abx and GF mice. Although the gut barrier in GF and Abx mice was disrupted, gut microbiota deficiency ameliorated the severity of AP, probably due to the reduction in bacterial translocation from the gut to the pancreas. The composition of the gut microbiota was significantly different between NLRP3 KO mice and wild-type (WT) mice at baseline, and there were alterations in response to the induction of AP. While a dramatic shift in the gut microbiota with overgrowth of was observed in WT mice suffering from AP, there was no significant change in NLRP3 KO mice with or without AP, suggesting that NLRP3 deficiency counteracts AP-induced microbial disturbance. With a strengthened gut barrier and decreased systemic inflammation, NLRP3 KO mice showed less severe AP, as revealed by reduced pancreatic neutrophilic infiltration and necrosis. Taken together, these results identified the bidirectional modulation between the gut microbiota and NLRP3 in the progression of AP, which suggests the interplay of the host and microbiome during AP.
肠道微生物群的早期失调与急性胰腺炎（AP）的严重程度有关，尽管其潜在机制尚不清楚。在这里，我们利用缺乏肠道微生物群的小鼠以及 NLRP3 敲除（KO）小鼠模型，研究了 NLRP3 和肠道微生物群之间的相互作用在 AP 发展中的作用。抗生素治疗（Abx）和无菌（GF）小鼠的胰腺损伤和全身炎症减轻，同时肠道 NLRP3 炎性体的活性减弱。有趣的是，粪便微生物群移植（FMT）重新激活了肠道 NLRP3 炎性体，并使 Abx 和 GF 小鼠的疾病恶化。尽管 GF 和 Abx 小鼠的肠道屏障被破坏，但肠道微生物群的缺乏改善了 AP 的严重程度，可能是由于从肠道到胰腺的细菌易位减少。NLRP3 KO 小鼠和野生型（WT）小鼠的基线肠道微生物群组成明显不同，并且对 AP 的诱导有反应。虽然在患有 AP 的 WT 小鼠中观察到肠道微生物群的剧烈变化和过度生长，但在有或没有 AP 的 NLRP3 KO 小鼠中没有明显变化，这表明 NLRP3 缺乏可对抗 AP 诱导的微生物失调。NLRP3 KO 小鼠的肠道屏障增强，全身炎症减轻，胰腺中性粒细胞浸润和坏死减少，表明 NLRP3 KO 小鼠的 AP 更严重。综上所述，这些结果确定了肠道微生物群和 NLRP3 之间在 AP 进展中的双向调节作用，提示宿主和微生物组在 AP 期间的相互作用。
