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Gut microbiota controls the development of chronic pancreatitis:A critical role of short-chain fatty acids-producing Gram-positive bacteria

引用

Acta Pharmaceutica Sinica B 2023年第10期13卷 4202-4216页

作者： Li-Long Pan Zheng-Nan Ren Jun Yang Bin-Bin Li Yi-Wen Huang Dong-Xiao Song Xuan Li Jia-Jia Xu Madhav Bhatia Duo-Wu Zou Chun-Hua Zhou Jia Sun Wuxi Medical School Jiangnan UniversityWuxi 214122China School of Food Science and Technology Jiangnan UniversityWuxi 214122China State Key Laboratory of Food Science and Resources Jiangnan UniversityWuxi 214122China Department of General Surgery Affiliated Hospital of Jiangnan UniversityWuxi 214122China Department of General Medicine Beicai Community Health Service Center of Pudong New DistrictShanghai 214001China Department of Pathology University of OtagoChristchurch 8140New Zealand Department of Gastroenterology Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disorder,accompanied by pancreatic exocrine insufficiency and dysregulated gut ***,accumulating evidence has supported a correlation between gut dysbiosis and CP ***,whether gut microbiota dysbiosis contributes to CP pathogenesis remains ***,an experimental CP was induced by repeated high-dose caerulein *** broad-spectrum antibiotics(ABX)and ABX targeting Gram-positive(G+)or Gram-negative bacteria(G-)were applied to explore the specific roles of these *** dysbiosis was observed in both mice and in CP patients,which was accompanied by a sharply reduced abundance for short-chain fatty acids(SCFAs)-producers,especially G+***-spectrum ABX exacerbated the severity of CP,as evidenced by aggravated pancreatic fibrosis and gut dysbiosis,especially the depletion of SCFAs-producing G+***,depletion of SCFAs-producing G+bacteria rather than G-bacteria intensified CP progression independent of TLR4,which was attenuated by supplementation with exogenous ***,SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype *** study supports a critical role for SCFAs-producing G+bacteria in ***,modulation of dietary-derived SCFAs or G+SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

关键词： Chronic pancreatitis Antibiotic exposure Gut microbiota Short-chain fatty acids-producing bacteria Pancreatic fibrogenesis macrophage responses Toll-like receptor 4

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