Beyond Digestion: The Pancreas Shapes Intestinal Microbiota and Immunity

Tilg, Herbert; Adolph, Timon E.

doi:10.1016/j.cmet.2017.02.018

Cited by 21 publications

(11 citation statements)

References 10 publications

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“…Among these factors, host genotype and diet seem to be the most important; furthermore, host and microbial genotypes influence cancer susceptibility. Notably, pancreatic acini can secret mediators that shape the gut microbiota and immunity [4].…”

Section: Introductionmentioning

confidence: 99%

The microbiota and microbiome in pancreatic cancer: more influential than expected

et al. 2019

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Microbiota is just beginning to be recognized as an important player in carcinogenesis and the interplay among microbes is greater than expected. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for which mortality closely parallels incidence. Early detection would provide the best opportunity to increase survival rates. Specific well-studied oral, gastrointestinal, and intrapancreatic microbes and some kinds of hepatotropic viruses and bactibilia may have potential etiological roles in pancreatic carcinogenesis, or modulating individual responses to oncotherapy. Concrete mechanisms mainly involve perpetuating inflammation, regulating the immune system-microbe-tumor axis, affecting metabolism, and altering the tumor microenvironment. The revolutionary technology of omics has generated insight into cancer microbiomes. A better understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy, adjustment of therapeutic efficacy even alleviating the adverse effects, creating new opportunities and fostering hope for desperate PDAC patients.

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Section: Introductionmentioning

confidence: 99%

The microbiota and microbiome in pancreatic cancer: more influential than expected

et al. 2019

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“…Considering the role of butyrate in promoting gut integrity and immune tolerance (Rooks and Garrett, 2016), this gut microbiota-derived metabolite appears as an attractive therapeutic candidate against T1D. Our studies and the literature highlight the beneficial relationships between the pancreas and the gut and this increasing knowledge should lead to identification of new approaches for the treatment of T1D (Tilg and Adolph, 2017). Limitation of the Study Our study describes a complex interplay between innate immune cells, pancreatic endocrine cells, and the intestinal microbiota, participating in the prevention of autoimmune diabetes in NOD mice.…”

Section: Discussionmentioning

confidence: 68%

Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes

et al. 2018

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The gut microbiota is essential for the normal function of the gut immune system, and microbiota alterations are associated with autoimmune disorders. However, how the gut microbiota prevents autoimmunity in distant organs remains poorly defined. Here we reveal that gut microbiota conditioned innate lymphoid cells (ILCs) induce the expression of mouse β-defensin 14 (mBD14) by pancreatic endocrine cells, preventing autoimmune diabetes in the non-obese diabetic (NOD) mice. MBD14 stimulates, via Toll-like receptor 2, interleukin-4 (IL-4)-secreting B cells that induce regulatory macrophages, which in turn induce protective regulatory T cells. The gut microbiota-derived molecules, aryl hydrocarbon receptor (AHR) ligands and butyrate, promote IL-22 secretion by pancreatic ILCs, which induce expression of mBD14 by endocrine cells. Dysbiotic microbiota and low-affinity AHR allele explain the defective pancreatic expression of mBD14 observed in NOD mice. Our study reveals a yet unidentified crosstalk between ILCs and endocrine cells in the pancreas that is essential for the prevention of autoimmune diabetes development.

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“…Several recent studies examined the changes in intestinal flora during AP development concerning disease severity. It is observed that abnormal trypsin secretion has occurred due to AP progression and that pancreatic structure destruction leads to an abnormal pancreatic secretion, resulting in the intestinal flora and homeostasis changes[ 76 , 77 ].…”

Section: Gut Microbiome and Microbiome In Apmentioning

confidence: 99%

“…Blocking acinar cell exocytosis in mice has been found to lead to gut dysbiosis, inflammation, systemic bacterial translocation, and ultimately, death. Additional evidence has revealed additional examples of crosstalk between pancreas acinar cells and the gut microbiome[ 76 , 77 ].…”

Section: Potential Role Of the Gut Microbiome In Apmentioning

confidence: 99%

Gut microbiome in acute pancreatitis: A review based on current literature

Patel¹,

Patel²,

Bhatia³

et al. 2021

WJG

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The gut microbiome is a complex microbial community, recognized for its potential role in physiology, health, and disease. The available evidence supports the role of gut dysbiosis in pancreatic disorders, including acute pancreatitis (AP). In AP, the presence of gut barrier damage resulting in increased mucosal permeability may lead to translocation of intestinal bacteria, necrosis of pancreatic and peripancreatic tissue, and infection, often accompanied by multiple organ dysfunction syndrome. Preserving gut microbial homeostasis may reduce the systemic effects of AP. A growing body of evidence suggests the possible involvement of the gut microbiome in various pancreatic diseases, including AP. This review discusses the possible role of the gut microbiome in AP. It highlights AP treatment and supplementation with prebiotics, synbiotics, and probiotics to maintain gastrointestinal microbial balance and effectively reduce hospitalization, morbidity and mortality in an early phase. It also addresses novel therapeutic areas in the gut microbiome, personalized treatment, and provides a roadmap of human microbial contributions to AP that have potential clinical benefit.

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Beyond Digestion: The Pancreas Shapes Intestinal Microbiota and Immunity

Cited by 21 publications

References 10 publications

The microbiota and microbiome in pancreatic cancer: more influential than expected

The microbiota and microbiome in pancreatic cancer: more influential than expected

Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes

Gut microbiome in acute pancreatitis: A review based on current literature

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