2’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathway
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...
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Tsinghua University Press
2024-09-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | https://www.sciopen.com/article/10.26599/FSHW.2022.9250205 |
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| author | Shikai Yan Leilei Yu Fengwei Tian Jianxin Zhao Wei Chen Qixiao Zhai |
| author_facet | Shikai Yan Leilei Yu Fengwei Tian Jianxin Zhao Wei Chen Qixiao Zhai |
| author_sort | Shikai Yan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c9c8b6dd1164466da591f9cc218cf2cb |
| institution | Kabale University |
| issn | 2097-0765 2213-4530 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-c9c8b6dd1164466da591f9cc218cf2cb2025-01-10T06:56:56ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302024-09-011352543256110.26599/FSHW.2022.92502052’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathwayShikai Yan0Leilei Yu1Fengwei Tian2Jianxin Zhao3Wei Chen4Qixiao Zhai5State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaImmune 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.https://www.sciopen.com/article/10.26599/FSHW.2022.92502052’-fucosyllactoseimmune checkpoint blockade-associated colitisgut microbiotametabolomicsregulatory t cells (treg) |
| spellingShingle | Shikai Yan Leilei Yu Fengwei Tian Jianxin Zhao Wei Chen Qixiao Zhai 2’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathway Food Science and Human Wellness 2’-fucosyllactose immune checkpoint blockade-associated colitis gut microbiota metabolomics regulatory t cells (treg) |
| title | 2’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathway |
| title_full | 2’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathway |
| title_fullStr | 2’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathway |
| title_full_unstemmed | 2’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathway |
| title_short | 2’-Fucosyllactose alleviate immune checkpoint blockade-associated colitis by reshaping gut microbiota and activating AHR pathway |
| title_sort | 2 fucosyllactose alleviate immune checkpoint blockade associated colitis by reshaping gut microbiota and activating ahr pathway |
| topic | 2’-fucosyllactose immune checkpoint blockade-associated colitis gut microbiota metabolomics regulatory t cells (treg) |
| url | https://www.sciopen.com/article/10.26599/FSHW.2022.9250205 |
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