Butyrate ameliorates caerulein‐induced acute pancreatitis and associated intestinal injury by tissue‐specific mechanisms

Pan, Xiaohua; Fang, Xin; Wang, Fei; Liu, Hongli; Niu, Wenying; Liang, Wenjie; Wu, Chengfei; Li, Jiahong; Tu, Xing; Pan, Li-Long; Sun, Jia

doi:10.1111/bph.14806

Cited by 107 publications

(85 citation statements)

References 62 publications

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“…19 Other studies in animal models also showed that improvements in the gut microbiota or supplementation with its metabolites ameliorated pancreatic injury by maintaining gut homeostasis. [20][21][22][23] Here, we observed that depletion of the gut microbiota reduced pancreatic damage and suppressed the systemic inflammatory response, while FMT reversed this process. 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.…”

Section: Discussionmentioning

confidence: 55%

“…Two other studies also detected the influence of the gut microbiota on the intestinal NLRP3 inflammasome during AP and demonstrated that pretreatment with probiotic Clostridium butyricum or its metabolite butyrate attenuates colonic injury and the inflammatory response by inhibiting the NLRP3 inflammasome pathway. 21,22 Thus, we hypothesize that the disturbance in the gut microbiota in the acute phase of AP stimulates intestinal inflammation via NLRP3 inflammasome activation, which contributes to the compromised epithelial barrier and facilitates the translocation of gut bacteria to distant organs. Therefore, the gut is not only the target organ in the development of AP but also the driver of complications in AP, especially IPN, which is always recognized as a second hit in the course of the disease.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

Gut Microbes

102

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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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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

Gut Microbes

102

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“…injections (one injection every hour for 10 h at a dose of 50 μg/kg). Animals were euthanized one hour after the last injection, and samples of blood, lung, and pancreatic tissue were collected for further study [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

“…Blood was collected and centrifuged, and the supernatant was used for measurement of serum amylase and lipase activities using respective commercial kits (Cusabio, Houston, TX, USA and Abcam, Cambrige, UK) (Cat.# CSB-EL001689MO and CSB-E16930m, respectively) [ 39 ]. Additionally, the plasma levels of interleukin 1 beta (IL-1β), IL-6 and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA) kits (eBioscience, San Diego, CA, USA) (Cat.# BMS6002, BMS603-2 and BMS607-3, respectively) as previously described [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

Cashew (Anacardium occidentale L.) Nuts Modulate the Nrf2 and NLRP3 Pathways in Pancreas and Lung after Induction of Acute Pancreatitis by Cerulein

et al. 2020

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Background: One of the most common co-morbidities, that often leads to death, associated with acute pancreatitis (AP) is represented by acute lung injury (ALI). While many aspects of AP-induced lung inflammation have been investigated, the involvement of specific pathways, such as those centered on nuclear factor E2-related factor 2 (Nrf2) and nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3 (NLRP3), has not been fully elucidated. Methods: To investigate the effect of cashew (Anacardium occidentale L.) nuts on pancreatic and lung injury induced by cerulein injection, cerulein (50 μg/kg) was administered to CD1 mice for 10 h. Oral treatment with cashew nuts at a dose of 100 mg/kg was given 30 min and 2 h after the first cerulein injection. One hour after the final cerulein injection, mice were euthanized and blood, lung and pancreatic tissue samples were collected. Results: Cashew nuts were able to (1) reduce histological damage; (2) mitigate the induction of mast cell degranulation as well as the activity of myeloperoxidase and malondialdehyde; (3) decrease the activity levels of amylase and lipase as well as the levels of pro-inflammatory cytokines; and (4) enhance the activation of the Nrf2 pathway and suppress the activation of the NLRP3 pathway in response to cerulein in both pancreas and lung. Conclusions: Cashew nuts could have a beneficial effect not only on pancreatitis but also on lung injury induced by cerulein.

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“…Acute pancreatitis is an inflammatory pathology characterized by elevation of serum pancreatic enzymes and acute abdominal pain [ 1 ]. Although the pancreas is primarily an exocrine gland, secreting a variety of digestive enzymes (trypsin, chymotrypsin and carboxypeptidase), it has an endocrine function.…”

Section: Introductionmentioning

confidence: 99%

Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury

et al. 2020

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Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 μg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut.

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Butyrate ameliorates caerulein‐induced acute pancreatitis and associated intestinal injury by tissue‐specific mechanisms

Cited by 107 publications

References 62 publications

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

Cashew (Anacardium occidentale L.) Nuts Modulate the Nrf2 and NLRP3 Pathways in Pancreas and Lung after Induction of Acute Pancreatitis by Cerulein

Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury

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