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

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 

机构地区：[1]Wuxi Medical School,Jiangnan University,Wuxi 214122,China [2]School of Food Science and Technology,Jiangnan University,Wuxi 214122,China [3]State Key Laboratory of Food Science and Resources,Jiangnan University,Wuxi 214122,China [4]Department of General Surgery,Affiliated Hospital of Jiangnan University,Wuxi 214122,China [5]Department of General Medicine,Beicai Community Health Service Center of Pudong New District,Shanghai 214001,China [6]Department of Pathology,University of Otago,Christchurch 8140,New Zealand [7]Department of Gastroenterology,Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第10期4202-4216,共15页药学学报（英文版）

基　　金：supported by funds from the National Natural Science Foundation of China(Grant Nos.82070666,82122068);the Natural Science Foundation for Distinguished Young Scholars of Jiangsu Province(Grant No.BK20200026,China);the Collaborative Innovation Center of Food Safety and Quality Control of Jiangsu Province,the Fundamental Research Funds for the Central Universities(Grant Nos.JUSRP221037,JUSRP22007,China);the China Postdoctoral Science Foundation(Grant No.2022M721366);the Excellent Postdoctoral Program of Jiangsu Province(Grant No.2023ZB168,China);Wuxi City’s first“double hundred”young and middle-aged medical and health talents(Grant No:BJ2020045,China);Wuxi Social Development Science and Technology Demonstration Project(Grant No:N20201003,China)。

摘　　要：Chronic pancreatitis(CP)is a progressive and irreversible fibroinflammatory disorder,accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota.Recently,accumulating evidence has supported a correlation between gut dysbiosis and CP development.However,whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear.Herein,an experimental CP was induced by repeated high-dose caerulein injections.The broad-spectrum antibiotics(ABX)and ABX targeting Gram-positive(G+)or Gram-negative bacteria(G-)were applied to explore the specific roles of these bacteria.Gut 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+bacteria.Broad-spectrum ABX exacerbated the severity of CP,as evidenced by aggravated pancreatic fibrosis and gut dysbiosis,especially the depletion of SCFAs-producing G+bacteria.Additionally,depletion of SCFAs-producing G+bacteria rather than G-bacteria intensified CP progression independent of TLR4,which was attenuated by supplementation with exogenous SCFAs.Finally,SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching.The study supports a critical role for SCFAs-producing G+bacteria in CP.Therefore,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 

分 类 号：R576[医药卫生—消化系统]