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硒干预对高脂饮食乳腺癌小鼠肠道微生物群稳态和基因功能的作用。

The role of selenium intervention in gut microbiota homeostasis and gene function in mice with breast cancer on a high-fat diet.

作者信息

Li Yinan, Liu Min, Kong Bingtan, Zhang Ganlin, Zhang Qing

机构信息

Beijing University of Chinese Medicine, Beijing, China.

Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

出版信息

Front Microbiol. 2024 Jul 31;15:1439652. doi: 10.3389/fmicb.2024.1439652. eCollection 2024.

Abstract

OBJECTIVE

This study aimed to investigate the effect of selenium on gut microbiota in mice with breast cancer under a high-fat diet.

METHODS

A total of 12 female BALB/c mice were randomly divided into two groups: 4 T1 + selenium+ high-fat diet group and 4 T1 + high-fat diet group. Mice were injected with 4 T1 cells on the right 4th mammary fat pad and kept on a high-fat diet. Fecal samples were collected, and DNA was extracted for metagenomic sequencing and bioinformatics analysis. Relevant target genes and pathways were annotated and metabolically analyzed to explore the intervention effect of selenium on breast cancer in the high-fat diet state.

RESULTS

Selenium supplementation in the high-fat diet altered the composition and diversity of gut microbiota in mice with breast cancer. The gut microbial composition was significantly different in the selenium intervention group, with an increased abundance of Proteobacteria, Actinobacteria, and Verrucomicrobia phyla and species such as , , and , while phyla, such as Bacteroidetes, Firmicutes, Deferribacteres, and Spirochaetes, and species, such as sp. , , , and sp. were decreased. Functional analysis revealed differential expression of genes related to carbohydrate-active enzymes, pathogen-host interactions, cell communication, cell auto-induction, membrane transporters, and virulence factors. Furthermore, 37 COGs and 48 metabolites with rising metabolic potential in the selenium intervention group were predicted.

CONCLUSION

Selenium alters the homeostasis of gut microbiota in mice with breast cancer on a high-fat diet, affecting their composition, abundance, and associated metabolism. These findings suggest that the mechanism involves interfering with gut microbiota homeostasis, leading to altered synthesis of tumor-associated proteins and fatty acids and inducing tumor cell apoptosis and pyroptosis.

摘要

目的

本研究旨在探讨硒对高脂饮食下乳腺癌小鼠肠道微生物群的影响。

方法

将12只雌性BALB/c小鼠随机分为两组:4T1 + 硒 + 高脂饮食组和4T1 + 高脂饮食组。将4T1细胞注射到小鼠右侧第4乳腺脂肪垫,并给予高脂饮食。收集粪便样本,提取DNA进行宏基因组测序和生物信息学分析。对相关靶基因和通路进行注释和代谢分析,以探讨硒在高脂饮食状态下对乳腺癌的干预作用。

结果

高脂饮食中补充硒改变了乳腺癌小鼠肠道微生物群的组成和多样性。硒干预组的肠道微生物组成有显著差异,变形菌门、放线菌门和疣微菌门以及诸如、和等物种的丰度增加,而拟杆菌门、厚壁菌门、脱铁杆菌门和螺旋体门以及诸如sp.、、和sp.等物种减少。功能分析显示与碳水化合物活性酶、病原体 - 宿主相互作用、细胞通讯、细胞自诱导、膜转运蛋白和毒力因子相关的基因表达存在差异。此外,预测了硒干预组中37个COG和48种代谢潜力增加的代谢物。

结论

硒改变了高脂饮食下乳腺癌小鼠肠道微生物群的稳态,影响其组成、丰度和相关代谢。这些发现表明其机制涉及干扰肠道微生物群稳态,导致肿瘤相关蛋白质和脂肪酸合成改变,并诱导肿瘤细胞凋亡和焦亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec39/11322145/03840799ba91/fmicb-15-1439652-g001.jpg

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