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初始肠道微生物群组成是口服铁补充剂促进结直肠癌的决定因素:来自小鼠模型的证据。

Initial gut microbiota composition is a determining factor in the promotion of colorectal cancer by oral iron supplementation: evidence from a murine model.

作者信息

Cuisiniere Thibault, Hajjar Roy, Oliero Manon, Calvé Annie, Fragoso Gabriela, Rendos Hervé Vennin, Gerkins Claire, Taleb Nassima, Gagnon-Konamna Marianne, Dagbert François, Loungnarath Rasmy, Sebajang Herawaty, Schwenter Frank, Wassef Ramses, Ratelle Richard, De Broux Éric, Richard Carole, Santos Manuela M

机构信息

Nutrition and Microbiome Laboratory, Centre de Recherche du Centre hospitalier de l', Université de Montréal (CRCHUM), Montréal, Québec, Canada.

Institut du Cancer de Montréal, Montréal, Québec, Canada.

出版信息

Microbiome. 2025 Apr 21;13(1):100. doi: 10.1186/s40168-025-02101-1.

DOI:10.1186/s40168-025-02101-1
PMID:40259408
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12013013/
Abstract

BACKGROUND

Colorectal cancer (CRC) development is influenced by both iron and gut microbiota composition. While iron supplementation is routinely used to manage anemia in CRC patients, it may also impact gut microbiota and promote tumorigenesis. In this study, we investigated the impact of initial gut microbiota composition on iron-promoted tumorigenesis. We performed fecal microbiota transplantation (FMT) in Apc mice using samples from healthy controls, CRC patients, and mice, followed by exposure to iron sufficient or iron excess diets.

RESULTS

We found that iron supplementation promoted CRC and resulted in distinct gut microbiota changes in Apc mice receiving FMT from CRC patients (FMT-CRC), but not from healthy controls or mice. Oral treatment with identified bacterial strains, namely Faecalibaculum rodentium, Holdemanella biformis, Bifidobacterium pseudolongum, and Alistipes inops, protected FMT-CRC mice against iron-promoted tumorigenesis.

CONCLUSIONS

Our findings suggest that microbiota-targeted interventions may mitigate tumorigenic effects of iron supplementation in anemic patients with CRC.

摘要

背景

结直肠癌(CRC)的发生受铁和肠道微生物群组成的影响。虽然常规使用铁补充剂来治疗CRC患者的贫血,但它也可能影响肠道微生物群并促进肿瘤发生。在本研究中,我们调查了初始肠道微生物群组成对铁促进的肿瘤发生的影响。我们使用来自健康对照、CRC患者和小鼠的样本对Apc小鼠进行粪便微生物群移植(FMT),然后使其暴露于铁充足或铁过量的饮食中。

结果

我们发现,补充铁促进了CRC的发生,并导致接受来自CRC患者的FMT(FMT-CRC)的Apc小鼠肠道微生物群发生明显变化,但接受来自健康对照或小鼠的FMT的Apc小鼠则没有。用鉴定出的细菌菌株,即啮齿类粪杆菌、双形霍尔德曼菌、假长双歧杆菌和无柄阿里斯杆菌进行口服治疗,可保护FMT-CRC小鼠免受铁促进的肿瘤发生。

结论

我们的研究结果表明,针对微生物群的干预措施可能减轻CRC贫血患者补充铁的致瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/c96719e0d5bc/40168_2025_2101_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/b6fb8dadda7b/40168_2025_2101_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/0776e54218e4/40168_2025_2101_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/fa5fb2374ca6/40168_2025_2101_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/141cc2c3bf83/40168_2025_2101_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/67f74e3fceda/40168_2025_2101_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/c96719e0d5bc/40168_2025_2101_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/b6fb8dadda7b/40168_2025_2101_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/0776e54218e4/40168_2025_2101_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/fa5fb2374ca6/40168_2025_2101_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/141cc2c3bf83/40168_2025_2101_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/67f74e3fceda/40168_2025_2101_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996f/12013013/c96719e0d5bc/40168_2025_2101_Fig6_HTML.jpg

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本文引用的文献

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Nutr Res Rev. 2025 Jun;38(1):229-237. doi: 10.1017/S0954422424000118. Epub 2024 Apr 8.
2
Gut Microbiome-Colorectal Cancer Relationship.肠道微生物群与结直肠癌的关系
Microorganisms. 2024 Feb 27;12(3):484. doi: 10.3390/microorganisms12030484.
3
Dose-Responsive Effects of Iron Supplementation on the Gut Microbiota in Middle-Aged Women.
铁补充剂对中年女性肠道微生物群的剂量反应影响。
Nutrients. 2024 Mar 10;16(6):786. doi: 10.3390/nu16060786.
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Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells.肿瘤微环境中的干扰素-γ促进结直肠癌细胞中 B7H4 的表达,从而抑制细胞毒性 T 细胞。
Sci Rep. 2024 Mar 13;14(1):6053. doi: 10.1038/s41598-024-56681-3.
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Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery.调节肠道微生物群可预防吻合口漏,减少结直肠癌手术后局部种植和播散。
Clin Cancer Res. 2024 Feb 1;30(3):616-628. doi: 10.1158/1078-0432.CCR-23-1601.
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The effect of iron therapy on oxidative stress and intestinal microbiota in inflammatory bowel diseases: A review on the conundrum.铁剂治疗对炎症性肠病氧化应激和肠道微生物群的影响:困境综述。
Redox Biol. 2023 Dec;68:102950. doi: 10.1016/j.redox.2023.102950. Epub 2023 Oct 30.
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High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice.高可溶性纤维通过调节小鼠肠道微生物群和代谢物促进结直肠肿瘤发生。
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Preoperative anemia and long-term survival in patients undergoing colorectal cancer surgery: a retrospective cohort study.术前贫血与结直肠癌手术患者的长期生存:一项回顾性队列研究。
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