The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice
The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice
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肠道微生物群和 NLRP3 激活之间的相互作用影响小鼠急性胰腺炎的严重程度
DOI：
10.1080/19490976.2020.1770042
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发表时间：
2020-11-01
期刊：
影响因子：
12.2
通讯作者：
Lu, Nonghua
中科院分区：
文献类型：
--
作者：
Li, Xueyang;He, Cong;Lu, Nonghua
摘要：肠道菌群的早期失调与急性胰腺炎（AP）的严重程度相关，但其潜在机制尚不清楚。在这里，我们利用肠道微生物群缺陷小鼠以及 NLRP3 敲除 (KO) 小鼠模型研究了 NLRP3 和肠道微生物群之间的串扰在 AP 发育中的作用。抗生素治疗（Abx）和无菌（GF）小鼠的胰腺损伤和全身炎症得到改善，同时肠道 NLRP3 炎症小体的活性减弱。有趣的是，粪便微生物群移植（FMT）重新激活了 Abx 和 GF 小鼠肠道 NLRP3 炎性体并加剧了疾病。尽管 GF 和 Abx 小鼠的肠道屏障被破坏，但肠道微生物群缺乏改善了 AP 的严重程度，这可能是由于从肠道到胰腺的细菌移位减少所致。 NLRP3 KO 小鼠和野生型 (WT) 小鼠的肠道微生物群组成在基线时存在显着差异，并且对 AP 的诱导反应也发生了变化。虽然在患有 AP 的 WT 小鼠中观察到肠道微生物群发生了巨大的变化，伴随着埃希氏菌-志贺氏菌的过度生长，但在患有或不患有 AP 的 NLRP3 KO 小鼠中，没有显着的变化，这表明 NLRP3 缺陷可以抵消 AP 诱导的微生物干扰。由于肠道屏障增强，全身炎症减少，NLRP3 KO 小鼠的 AP 严重程度减轻，这通过胰腺中性粒细胞浸润和坏死减少来体现。综上所述，这些结果确定了 AP 进展过程中肠道微生物群和 NLRP3 之间的双向调节，这表明 AP 期间宿主和微生物组之间的相互作用。
ABSTRACT 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 Escherichia-Shigella 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.