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Open Access

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

Shikai Yana,b, Leilei Yua,b, Fengwei Tiana,b, Jianxin Zhaoa,b, Wei Chena,b,c, Qixiao Zhaia,b( )
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

Peer review under responsibility of Tsinghua University Press.

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Graphical Abstract

Abstract

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 f indings suggest that 2’FL could serve as a potential protective strategy for ICB-associated colitis by modulating the intestinal microbiota and bacterial metabolites.

Keywords

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

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Food Science and Human Wellness
Volume 13 Issue 5,
September 2024
Pages 2543-2561
DOI: 10.26599/FSHW.2022.9250205
Cite this article:
Yan S, Yu L, Tian F, et al. 2’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathway. Food Science and Human Wellness, 2024, 13(5): 2543-2561. https://doi.org/10.26599/FSHW.2022.9250205

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Received: 16 February 2023
Revised: 28 February 2023
Accepted: 01 March 2023
Published: 10 October 2024
© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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