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

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外文摘要：Immune checkpoint blockade(ICB)therapeutics are highly effective in cancer immunotherapy,but gastrointestinal toxicity limited the application.Intestinal 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 effect.The study aimed to determine the effects of 2'FL on ICB-associated colitis and to uncover the mediating mechanism.ICB-associated colitis was induced by the ipilimumab and dextran sulfate sodium.Oral 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)pathway.The protective effect of 2'FL was abolished upon depletion of gut microbiota,and ILA treatment partially simulated the protective effect of 2'FL.Notably,2'FL did not exhibit inhibition of antitumor immunity.These findings suggest that 2'FL could serve as a potential protective strategy for ICB-associated colitis by modulating the intestinal microbiota and bacterial metabolites.

外文关键词：

2'-FucosyllactoseImmune checkpoint blockade-associated colitisGut microbiotaMetabolomicsRegulatory T cells(Treg)

作者：

Shikai Yan、Leilei Yu、Fengwei Tian、Jianxin Zhao、Wei Chen、Qixiao Zhai

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作者单位：

State Key Laboratory of Food Science and Technology,Jiangnan University,Wuxi 214122,China

School of Food Science and Technology,Jiangnan University,Wuxi 214122,China

National Engineering Research Center for Functional Food,Jiangnan University,Wuxi 214122,China

基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaCollaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province

项目编号：

3212206732021005

出版年：

2024

DOI：

10.26599/FSHW.2022.9250205

食品科学与人类健康(英文)

CSTPCD

ISSN：

年,卷(期)：2024.13(5)