Bile acid supplementation improves murine pancreatitis in association with the gut microbiota
| Autor: | Rui-Xue Zhu, You-Dong Wan, Xinting Pan, Tong-Wen Sun |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
intestinal microbiota
medicine.medical_specialty Physiology medicine.drug_class pancreatitis Gut flora Fibroblast growth factor digestive system lcsh:Physiology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Physiology (medical) 16S rDNA Internal medicine microbiota Medicine Receptor Barrier function Original Research bile acids lcsh:QP1-981 Bile acid biology business.industry Tauroursodeoxycholic acid medicine.disease biology.organism_classification Endocrinology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Pancreatitis 030211 gastroenterology & hepatology business Pancreas |
| Zdroj: | Frontiers in Physiology Frontiers in Physiology, Vol 11 (2020) |
| Popis: | 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 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. Similar results were found in microbiota-depleted AP without BA treatment. However, we did not observe further downregulation of the FXR signaling pathway in microbiota-depleted AP mice given TUDCA, indicating that improvement of pancreatitis by TUDCA may be associated with gut microbiota. Our analysis of changes to the gut microbiota in AP indicated that Lactobacilli may be the key contributors. Taken together, our study shows that supplementation with BAs could improve bile acid-FXR-FGF15 signaling, and reduce pancreatic and intestinal injury, and that this effect may be associated with the gut microbiota. |
| Databáze: | OpenAIRE |
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