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

Li, Xueyang, He, Cong, Li, Nianshuang, Ding, Ling, Chen, Hongyan, Wan, Jianhua, Yang, Xiaoyu, Xia, Liang, He, Wenhua ORCID: 0000-0001-5499-1346, Xiong, Huifang
et al (show 3 more authors) (2020) The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice. GUT MICROBES, 11 (6). pp. 1774-1789.

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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 <i>Escherichia-Shigella</i> 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.

Item Type: Article
Uncontrolled Keywords: Acute pancreatitis, gut microbiota, NLRP3, gut barrier, inflammation
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 13 Jul 2021 13:20
Last Modified: 18 Jan 2023 21:36
DOI: 10.1080/19490976.2020.1770042
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