Intestinal homeostasis and inflammation: Gut microbiota at the crossroads of pancreas–intestinal barrier axis

Zhang, Zhongwei; Izumi, Tohru; Zhang, Pan; Ernst, Peter B.; Kurashima, Yosuke

doi:10.1002/eji.202149532

Cited by 24 publications

(18 citation statements)

References 133 publications

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“…Intestinal homeostasis is disturbed during AP progression which could lead to bacteria translocation, systemic inflammatory response syndrome (SIRS), and multiple organ dysfunction syndromes (MODS) 1,4,41 . Therefore, many studies devoted to explore the mechanism underlying the intestinal barrier dysfunction during AP.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis

Yin,

Xu,

Huang

et al. 2024

The FASEB Journal

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Intestinal barrier dysfunction usually occurred in acute pancreatitis (AP) but the mechanism remains unclear. In this study, RNA sequencing of ileum in L‐arginine‐induced AP mice demonstrated that phosphoenolpyruvate kinase 1 (Pck1) was significantly up‐regulated. Increased Pck1 expression in intestinal epithelial cells (IECs) was further validated in ileum of AP mice and duodenum of AP patients. In AP mice, level of Pck1 was positively correlated with pancreatic and ileal histopathological scores, serum amylase activity, and intestinal permeability (serum diamine oxidase (DAO), D‐lactate, and endotoxin). In AP patients, level of Pck1 had a positive correlation with Ranson scores, white blood cell count and C‐reactive protein. Inhibition of Pck1 by 3‐Mercaptopicolinic acid hydrochloride (3‐MPA) alleviated pancreatic and ileal injuries in AP mice. AP + 3‐MPA mice showed improved intestinal permeability, including less epithelial apoptosis, increased tight junction proteins (TJPs) expression, decreased serum DAO, D‐lactate, endotoxin, and FITC‐Dextran levels, and reduced bacteria translocation. Lysozyme secreted by Paneth cells and mucin2 (MUC2) secretion in goblet cells were also partly restored in AP + 3‐MPA mice. Meanwhile, inhibition of Pck1 improved intestinal immune response during AP, including elevation of M2/M1 macrophages ratio and secretory immunoglobulin A (sIgA) and reduction in neutrophils infiltration. In vitro, administration of 3‐MPA dramatically ameliorated inflammation and injuries of epithelial cells in enteroids treated by LPS. In conclusion, inhibition of Pck1 in IECs might alleviate AP via modulating intestinal homeostasis.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis

Yin,

Xu,

Huang

et al. 2024

The FASEB Journal

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“…The pancreas performs digestive and endocrine functions. The pancreas secretes secretory phospholipase A2, pancreatic lipase, and glycoprotein 2 to protect the gut and maintain the ora through bacterial lysis [17]. Conversely, the gut can in uence pancreatic endocrine function through vasoactive intestinal peptides such as secretin, glucagon-releasing peptide, and growth inhibitor [18].…”

Section: Discussionmentioning

confidence: 99%

The causal association between inflammatory bowel disease and pancreatitis: a two-sample Mendelian randomization study

Gao,

Zhang,

Cai

et al. 2023

Preprint

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Background Clinical studies showed a relationship between inflammatory bowel disease (IBD) and pancreatitis. This study employed a Mendelian randomization (MR) approach to determine whether there is a causal association between IBD and pancreatitis. Methods Genome-wide association study data on IBD were acquired from the International Inflammatory Bowel Disease Genetics Consortium. Summary statistics for acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced acute pancreatitis (AAP), and alcohol-induced chronic pancreatitis (ACP) were from the FinnGen database. Inverse-variance weighting (IVW) was used to perform a two-sample MR analysis. Heterogeneity tests, horizontal pleiotropy tests, and sensitivity analyses were used to ensure the consistency and accuracy of our results. Results The incidence of AP in IBD populations was 1.063 times higher than in the control population (95% confidence interval [CI]: 1.008–1.121, IVW p = 0.023). The CP incidence in IBD populations was 1.075 times higher than in the comparative population (95% CI: 1.004–1.153, IVW p = 0.039). AP incidence in Crohn’s disease (CD) populations was 1.056 times higher than in the comparative population (95% CI: 1.010–1.105, IVW p = 0.017). The CP incidence in CD populations was approximately 1.070 times higher than in the comparative population (95% CI: 1.009–1.135, IVW p = 0.024). AP incidence in ulcerative colitis (UC) populations was 1.070 folds higher than in the general population (95% CI: 1.007–1.137, IVW p = 0.030), AAP incidence in UC populations was 1.189 times higher than in the general population (95% CI: 1.009–1.135, IVW p = 0.024). Conclusion IBD increases the risk of AP and CP. CD was related to AP and CP. UC had a causality with AP and AAP. Our research verified that IBD increased the risk of pancreatitis.

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“…This contributed to inhibited bacterial translocation. In addition, Bifidobacterium , a popular intestinal probiotic, can reduce the gastrointestinal dysfunction [ 40 ]. Bacteroides enhance the differentiation of goblet cells, leading to an increase in the number of goblet cells and mucin gene expression in the colon of gnotobiotic rats [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…Local homeostasis is disturbed when gut bacteria translocate into the pancreas. An E. coli MG1655 mono-colonized pancreatitis rat model demonstrated more severe pancreatic injury as compared to a normal pancreatitis rat model with significant upregulation of the TLR-4-mitogen-activated protein pathway and activation of the ERS pathway in intestinal epithelial cells [ 40 ]. NLPR3 may be a crucial factor in the gut microbiota-pancreatitis axis [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Surfactin Mitigates a High-Fat Diet and Streptozotocin-Induced Type 2 Diabetes through Improving Pancreatic Dysfunction and Inhibiting Inflammatory Response

Chen

Zhao

et al. 2022

IJMS

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Surfactin from Bacillus amyloliquefaciens fmb50 was utilized to treat mice with type 2 diabetes (T2DM) induced by a high-fat diet/streptozotocin (HFD/STZ). Our group’s earlier research indicated that surfactin could lower blood glucose and mitigate liver dysfunction to further improve HFD/STZ-induced T2DM through modulating intestinal microbiota. Thus, we further investigated the effects of surfactin on the pancreas and colon in mice with T2DM to elucidate the detailed mechanism. In the present study, mice with HFD/STZ-induced T2DM had their pancreatic and colon inflammation, oxidative stress, and endoplasmic reticulum stress (ERS) reduced when given oral surfactin at a dose of 80 mg/kg body weight. According to further research, surfactin also improved glucose metabolism by activating the phosphatidylinositol kinase (PI3K)/protein kinase B (Akt) signaling pathway, further protecting islets β-cell, promoting insulin secretion, inhibiting glucagon release and mitigating pancreas dysfunction. Additionally, after surfactin treatment, the colon levels of the tight junction proteins Occludin and Claudin-1 of T2DM mice were considerably increased by 130.64% and by 36.40%, respectively. These findings revealed that surfactin not only ameliorated HFD/STZ-induced pancreas inflammation and dysfunction and preserved intestinal barrier dysfunction and gut microbiota homeostasis but also enhanced insulin sensitivity and glucose homeostasis in T2DM mice. Finally, in the further experiment, we were able to demonstrate that early surfactin intervention might delay the development of T2DM caused by HFD/STZ, according to critical biochemical parameters in serum.

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Intestinal homeostasis and inflammation: Gut microbiota at the crossroads of pancreas–intestinal barrier axis

Cited by 24 publications

References 133 publications

Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis

Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis

The causal association between inflammatory bowel disease and pancreatitis: a two-sample Mendelian randomization study

Surfactin Mitigates a High-Fat Diet and Streptozotocin-Induced Type 2 Diabetes through Improving Pancreatic Dysfunction and Inhibiting Inflammatory Response

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