南昌大学第一附属医院:肠道菌群与NLRP3炎性小体互作调控急性胰腺炎
创作:szx 审核:szx 06月23日
  • 诱导小鼠的AP 36h后,肠道通透性增加且菌群组成失调,大肠杆菌向胰腺的易位增加,肠道NLRP3炎性小体活化增强;
  • 诱导7天后,随着AP的逐渐缓解,肠道通透性、菌群组成及NLRP3炎性小体活化均趋于恢复正常;
  • 抗生素处理或使用无菌小鼠可缓解AP的严重程度,并抑制肠道NLRP3炎性小体的活化及大肠杆菌向胰腺的易位,但通过粪菌移植重新定殖菌群可逆转;
  • 敲除NLRP3可缓解AP,并抑制AP诱导的肠道通透性增加、菌群失调及大肠杆菌向胰腺的易位。
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szx
肠道菌群失调与急性胰腺炎(AP)的严重程度相关,但背后的机制尚未明确。来自南昌大学第一附属医院的Yin Zhu团队在《Gut Microbes》上发表的一项最新研究,发现在诱导的AP小鼠模型中,AP可导致肠道菌群失调、肠道屏障受损、菌群向胰腺易位增加及肠道NLRP3炎性小体活化增强,而去除菌群(抗生素处理或使用无菌小鼠)或敲除NLRP3,均可缓解AP,并抑制AP诱导的上述表型变化。该研究结果提示,肠道菌群与NLRP3炎性小体的互作在AP的进展中起到重要调控作用。
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Gut Microbes [IF:7.74]

The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice

肠道菌群与NLRP3活化之间的互作影响小鼠急性胰腺炎的严重程度

10.1080/19490976.2020.1770042

06-12, Article

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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.

First Authors:
Xueyang Li,Cong He

Correspondence Authors:
Yin Zhu

All Authors:
Xueyang Li,Cong He,Nianshuang Li,Ling Ding,Hongyan Chen,Jianhua Wan,Xiaoyu Yang,Liang Xia,Wenhua He,Huifang Xiong,Xu Shu,Yin Zhu,Nonghua Lu

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