Gut microbiota-derived tryptophan metabolites regulated by Wuji Wan to attenuate colitis through AhR signaling activation  

作　　者：Wanghui Jing Sijing Dong Yinyue Xu Jingjing Liu Jiawei Ren Xue Liu Min Zhu Menggai Zhang Hehe Shi Na Li Peng Xia Haitao Lu Sicen Wang 

机构地区：[1]School of Pharmacy,Health Science Center,Xi’an Jiaotong University,Xi’an 710061,China [2]Shaanxi Engineering Research Center of Cardiovascular Drugs Screening&Analysis,Xi’an 710061,China [3]Department of Medicament,College of Medicine,Tibet University,Lhasa 850012,China [4]Department of Surgical Oncology,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China [5]School of Chinese Medicine,Hong Kong Traditional Chinese Medicine Phenome Center,State Key Laboratory of Environmental and Biological Analysis,Hong Kong Baptist University,Hong Kong 999077,China [6]Shanghai Institute of Hematology,State Key Laboratory of Medical Genomics,National Research Center for Translational Medicine at Shanghai,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [7]Key Laboratory of Systems Biomedicine(Ministry of Education),Shanghai Center for Systems Biomedicine,Shanghai Jiao Tong University,Shanghai 200240,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第1期205-223,共19页药学学报(英文版)

基　　金：supported by the National Natural Scientific Foundation of China(82174059);Outstanding young and middleaged science and technology talents of Shaanxi Administration of Traditional Chinese Medicine(2023-ZQNY-004,China);the Natural Science Foundation of Shaanxi Province(2022SF-123,China);Innovative talent team introduction project in Xinzhou City(20220701,China);the Project of Shaanxi Administration of Traditional Chinese Medicine(No.2022-SLRH-YQ-001,China);the SKL-GRF Grant from State Key Laboratory of Environmental and Biological Analysis at Hong Kong Baptist University(SKLP_2425_P02,China).

摘　　要：Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease(IBD).Traditional Chinese medicine Wuji Wan(WJW)is commonly used to treat digestive system disorders and showed therapeutic potential for IBD.In this interdisciplinary study,we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques.Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus,thereby facilitating the conversion of tryptophan into indole-3-acetic acid(IAA)and indoleacrylic acid(IA).These indole derivatives activated the aryl hydrocarbon receptor(AhR)pathway,which reduced colonic inflammation and restored the expression of intestinal barrier proteins.Interestingly,the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota.Finally,pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW.Overall,WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating LactobacilluseIAAeAhR signaling pathway.This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

关 键 词：Wuji Wan COLITIS Gut microbiota Tryptophan metabolite Intestinal barrier Aryl hydrocarbon receptor Indole-3-acetic acid 

分 类 号：R57[医药卫生—消化系统]