Commensal
            <i>Escherichia coli</i>
            Aggravates Acute Necrotizing Pancreatitis through Targeting of Intestinal Epithelial Cells

Zheng, Jie; Lou, Lihong; Fan, Jie; Huang, Chen; Mei, Qixiang; Wu, Jianghong; Guo, Yuecheng; Lǚ, Yingying; Wang, Xingpeng; Zeng, Yue

doi:10.1128/aem.00059-19

Cited by 50 publications

(42 citation statements)

References 32 publications

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“…It is possible that a bloom of mucus-degrading bacteria, such as A. muciniphila , may play a part in the known mucosal damage and altered intestinal integrity that develops in clinical and experimental pancreatitis 36 , 37 . In line with previous work 1 , 3 , 4 , 38 , 39 an increase of the Escherichia / Shigella genus in some gut compartments was noticed, implying a potential pathogenic role in this model of necrotizing pancreatitis. The majority of pathogens cultured in infected pancreatic collections (among others Escherichia coli and P. mirabilis ) are known gut inhabitants that are thought to translocate and cause (extra-) pancreatic infections 40 , 41 .…”

Section: Discussionsupporting

confidence: 92%

Spatioregional assessment of the gut microbiota in experimental necrotizing pancreatitis

et al. 2021

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Background Infectious complications following experimental pancreatitis involve major disruptions in the gut microbiota. The aim of this study was to characterize this disruption by examining the spatioregional distribution in microbial community structure and function following experimental pancreatitis associated with pancreatic infection. Methods Mice were subjected to infusion of the pancreatic duct with either taurocholate to induce necrotizing pancreatitis or normal saline (control group). The spatial (lumen versus mucosa) and regional composition and function of the microbiota from the duodenum, ileum, caecum, colon, pancreas and blood were evaluated using 16S rRNA gene amplicon sequencing. Results Mice that developed necrotizing pancreatitis demonstrated a decrease in microbial richness and significantly altered microbiota in distal parts of the gastrointestinal tract, compared with controls. Among the most differentially increased taxa were the mucus-degrading Akkermansia muciniphila, and there was a decrease of butyrate-producing bacteria following pancreatitis. Application of the SourceTracker tool to the generated metadata indicated that the duodenum was the most probable source of bacteria that subsequently infected pancreatic tissue in this model. The functional prediction annotation using pathway analyses indicated a diminished capacity of the caecal microbiota to metabolize carbohydrate, and fatty and amino acids. Discussion The distal gut microbiota was significantly impacted in this model of experimental necrotizing pancreatitis. Data suggest that the duodenal microbiota might also play a role in bacterial translation and secondary infections.

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Section: Discussionsupporting

confidence: 92%

Spatioregional assessment of the gut microbiota in experimental necrotizing pancreatitis

et al. 2021

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“…This finding was consistent with previous studies that showed a protective effect of antibiotics on AP, and this protective effect was weakened after transplanting gut commensal bacteria. 11,12 However, the molecular mechanisms underlying the crosstalk between the gut microbiota and pancreas are not well understood.…”

Section: Discussionmentioning

confidence: 99%

“…8 Furthermore, antibiotic treatment protects mice from caerulein-induced pancreatic injury and systemic inflammation, indicating the role of the gut microbiota in the development of AP. 11,12 Nod-like receptors (NLRs) are intracellular pattern recognition molecules that detect microbialand danger-associated molecular patterns. NLRP3, one of the NLR proteins, plays an important role in forming inflammasomes, which mediate caspase-1 activation and the secretion of the proinflammatory cytokine IL-1β in response to microbial infection and cellular damage.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

Gut Microbes

101

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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.

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“…Zhu et al (2019) found that increased capacity for bacterial invasion of epithelial cells in AP correlated closely with the abundance of Escherichia-Shigella in fecal samples from 165 adults. Zheng et al (2019) showed that commensal Escherichia coli MG1655 increases TLR4/MyD88/p38 MAPK and ERS signaling-induced intestinal epithelial injury and aggravates AP in rats. These authors inferred gut microbiota dysbiosis in AP and tried to explain it from different perspectives.…”

Section: Discussionmentioning

confidence: 99%

Bile Acid Supplementation Improves Murine Pancreatitis in Association With the Gut Microbiota

2020

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Disorders of bile acids (BAs) are closely related to the development of liver and intestinal diseases, including acute pancreatitis (AP). However, the mechanism underlying the involvement of BAs in AP development remains unclear. We used intraperitoneal injection of cerulein to construct AP mouse models. These mice had significantly reduced tauroursodeoxycholic acid (TUDCA) and an imbalance of intestinal microbiota, based on 16S rDNA gene sequencing. To explore the role of AP-induced intestinal microbiota changes in the development of AP, we transplanted the stool obtained from AP mice to antibiotic-treated, microbiota-depleted healthy mice. Microbiota-depleted mice presented injury to the intestinal barrier function and pancreas. Additionally, microbiota depletion reduced AP-associated pancreatic injury. This indicated that the gut microbiota may worsen AP. As TUDCA was deficient in AP mice, we gavaged AP mice with it, and evaluated subsequent expression changes in the bile acid signaling receptors farnesoid-x-receptor (FXR) and its target gene fibroblast growth factor (FGF) 15. These were downregulated, and pancreatic and intestinal barrier function injury were mitigated. The gut microbiota is known to regulate bile acid production and signaling, and our analysis of changes to the gut microbiota in AP indicated that Lactobacilli may be the key contributors of TUDCA. Taken together, our study shows that supplementation with BAs could reduce pancreatic and intestinal injury, and that this effect may be associated with the gut microbiota.

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Commensal Escherichia coli Aggravates Acute Necrotizing Pancreatitis through Targeting of Intestinal Epithelial Cells

Cited by 50 publications

References 32 publications

Spatioregional assessment of the gut microbiota in experimental necrotizing pancreatitis

Spatioregional assessment of the gut microbiota in experimental necrotizing pancreatitis

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

Bile Acid Supplementation Improves Murine Pancreatitis in Association With the Gut Microbiota

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