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Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration

文献类型：期刊论文

作者Wang, Li-juan4; Jin, Yuan-ling4; Pei, Wen-long3; Li, Jia-cong4; Zhang, Rui-lin4; Wang, Jia-ju4; Lin, Wei1,2,4
刊名ACTA PHARMACOLOGICA SINICA
出版日期2023-11-27
页码11
关键词acute pancreatitis Amuc_1100 inflammation gut microbiota tryptophan metabolism
ISSN号1671-4083
DOI10.1038/s41401-023-01186-4
通讯作者Wang, Li-juan(lucywang2012@163.com) ; Lin, Wei(weilin@njucm.edu.cn)
英文摘要Amuc_1100 is a membrane protein from Akkermansia muciniphila, which has been found to play a role in host immunological homeostasis in the gastrointestinal tract by activating TLR2 and TLR4. In this study we investigated the effects and underlying mechanisms of Amuc_1100 on acute pancreatitis (AP) induced in mice by intraperitoneal injection of caerulein and lipopolysaccharide (LPS). The mice were treated with the protein Amuc_1100 (3 mu g, i.g.) for 20 days before caerulein injection. Cecal contents of the mice were collected for 16S rRNA sequencing. We found that pretreatment with Amuc_1100 significantly alleviated AP-associated pancreatic injury, reduced serum amylase and lipase. Amuc_1100 pretreatment significantly inhibited the expression of proinflammatory cytokines (TNF-alpha, IL-1 beta, IFN-gamma and IL-6) in spleen and pancreas through inhibiting NF-kappa B signaling pathway. Moreover, Amuc_1100 pretreatment significantly decreased the inflammatory infiltration, accompanied by the reduction of Ly6C+ macrophages and neutrophils in the spleen of AP mice. Gut microbiome analysis showed that the abundance of Bacteroidetes, Proteobacteria, Desulfobacterota and Campilobacterota was decreased, while the proportion of Firmicutes and Actinobacteriota was increased in AP mice pretreated with Amuc_1100. We further demonstrated that Amuc_1100 pretreatment restored the enrichment of tryptophan metabolism, which was mediated by intestinal flora. These results provide new evidence that Amuc_1100 lessens the severity of AP through its anti-inflammatory properties with a reduction of macrophages and neutrophil infiltration, as well as its regulation of the composition of intestinal flora and tryptophan metabolism.
WOS关键词DYSBIOSIS ; SEVERITY
资助项目National Natural Science Foundations of China[32270192] ; National Natural Science Foundations of China[82072240] ; Open Funding Project of the State Key Laboratory of Bioreactor Engineering ; Open Project of the State Key Laboratory of Drug Research ; Shanghai Institute of Materia Medica ; Chinese Academy of Sciences[SIMM2205KF-15] ; Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine[2020YLXK008] ; Natural Science Foundation of Jiangsu Province of China[BK20230064] ; Fok Ying Tung Education Foundation[171033] ; High level key discipline construction project of the National Administration of Traditional Chinese Medicine-Resource Chemistry of Chinese Medicinal Materials[zyyzdxk-2023083]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001114772300001
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/308080]  
专题新药研究国家重点实验室
通讯作者Wang, Li-juan; Lin, Wei
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China
3.Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Nanjing 211166, Peoples R China
4.Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Dept Pathogen Biol, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Li-juan,Jin, Yuan-ling,Pei, Wen-long,et al. Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration[J]. ACTA PHARMACOLOGICA SINICA,2023:11.
APA Wang, Li-juan.,Jin, Yuan-ling.,Pei, Wen-long.,Li, Jia-cong.,Zhang, Rui-lin.,...&Lin, Wei.(2023).Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration.ACTA PHARMACOLOGICA SINICA,11.
MLA Wang, Li-juan,et al."Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration".ACTA PHARMACOLOGICA SINICA (2023):11.

入库方式： OAI收割

来源：上海药物研究所

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