2’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathway

作     者：Shikai Yan Leilei Yu Fengwei Tian Jianxin Zhao Wei Chen Qixiao Zhai Shikai Yan;Leilei Yu;Fengwei Tian;Jianxin Zhao;Wei Chen;Qixiao Zhai

作者机构：State Key Laboratory of Food Science and TechnologyJiangnan UniversityWuxi 214122China School of Food Science and TechnologyJiangnan UniversityWuxi 214122China National Engineering Research Center for Functional FoodJiangnan UniversityWuxi 214122China 

出 版 物：《Food Science and Human Wellness》 (食品科学与人类健康（英文）)

年 卷 期：2024年第13卷第5期

页      面：2543-2561页

核心收录：

学科分类：0832[工学-食品科学与工程（可授工学、农学学位）] 08[工学] 083201[工学-食品科学] 

基　　金：supported by the National Natural Science Foundation of China(32122067) the National Natural Science Foundation of China(32021005) Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province 

主　　题：2’-Fucosyllactose Immune checkpoint blockade-associated colitis Gut microbiota Metabolomics Regulatory T cells(Treg) 

摘      要：Immune checkpoint blockade(ICB)therapeutics are highly effective in cancer immunotherapy,but gastrointestinal toxicity limited the *** microbiota plays a crucial role in ICB-associated colitis.2’-Fucosyllactose(2’FL)is most abundance prebiotic in human milk that can reshape gut microbiota and exert immune regulatory *** study aimed to determine the effects of 2’FL on ICB-associated colitis and to uncover the mediating ***-associated colitis was induced by the ipilimumab and dextran sulfate *** administration of 2’FL(0.6 g/(kg∙day))ameliorated ICB-induced colitis by enhancing regulatory T cells(Treg)and the M2/M1 ratio of macrophages in colon.2’FL treatment also increased the expression of tight junction proteins(zonula occludens-1(ZO-1)and mucin 2(MUC2))and antioxidant stress indicators(superoxide dismutase(SOD)and catalase(CAT)).In addition,administration of 2’FL increased the abundance of Bifidobacterium and Lactobacillus,and elevated the levels of microbial metabolites,such as indole-3-lactic acid(ILA),which activated the aryl hydrocarbon receptor ligands(AHR)*** protective effect of 2’FL was abolished upon depletion of gut microbiota,and ILA treatment partially simulated the protective effect of 2’***,2’FL did not exhibit inhibition of antitumor *** findings suggest that 2’FL could serve as a potential protective strategy for ICB-associated colitis by modulating the intestinal microbiota and bacterial metabolites.