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用益生菌双歧三联活菌预处理可改善小鼠结肠炎相关癌症:转录组和肠道菌群分析

Pretreatment with probiotic Bifico ameliorates colitis-associated cancer in mice: Transcriptome and gut flora profiling.

作者信息

Song Huan, Wang Weiyi, Shen Bo, Jia Hao, Hou Zhaoyuan, Chen Ping, Sun Yunwei

机构信息

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cellular Biology, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Cancer Sci. 2018 Mar;109(3):666-677. doi: 10.1111/cas.13497. Epub 2018 Feb 14.

Abstract

Individuals with inflammatory bowel disease are at high risk of developing colitis-associated cancer (CAC). Strategies to block the process from inflammatory bowel disease to CAC should be considered. In the experiment, we aim to explore the chemopreventive efficacy of the probiotic cocktail Bifico and its potential mechanism in azoxymethane and dextran sodium sulphate-induced CAC in mice. Oral pretreatment of Bifico was adopted to evaluate its protective effect. The colorectums of 35 C57BL/6 mice were collected and examined for the degree of inflammation and tumorigenesis. Comparative 16S rRNA sequencing was carried out to observe Bifico-target alterations in gene expression and microbiota structure. We found that pretreatment of Bifico alleviated intestinal inflammation and reduced tumor formation. Furthermore, we identified a subset of genes as potential targets of Bifico treatment, including CXCL1, CXCL2, CXCL3, and CXCL5, which are all ligands of C-X-C motif receptor 2 (CXCR2). The 16S rRNA sequencing showed that Bifico decreased the abundance of genera Desulfovibrio, Mucispirillum, and Odoribacter, and a bloom of genus Lactobacillus was detected. Notably, we found that an abundance of these Bifico-target taxa was significantly associated with the expression of CXCR2 ligand genes. Our studies indicate that Bifico, given orally, can ameliorate CAC in mice through intervening with the possible link between Desulfovibrio, Mucispirillum, Odoribacter, Lactobacillus, and CXCR2 signaling.

摘要

炎症性肠病患者患结肠炎相关癌症(CAC)的风险很高。应考虑采取措施阻断从炎症性肠病到CAC的进程。在本实验中,我们旨在探讨益生菌组合贝飞达在小鼠中对由氧化偶氮甲烷和葡聚糖硫酸钠诱导的CAC的化学预防效果及其潜在机制。采用口服贝飞达预处理来评估其保护作用。收集35只C57BL/6小鼠的结肠直肠,检查炎症程度和肿瘤发生情况。进行比较性16S rRNA测序以观察贝飞达靶向的基因表达和微生物群结构变化。我们发现贝飞达预处理减轻了肠道炎症并减少了肿瘤形成。此外,我们确定了一组基因作为贝飞达治疗的潜在靶点,包括CXCL1、CXCL2、CXCL3和CXCL5,它们都是C-X-C基序受体2(CXCR2)的配体。16S rRNA测序表明,贝飞达降低了脱硫弧菌属、黏液螺旋菌属和气味杆菌属的丰度,并检测到乳酸杆菌属的大量繁殖。值得注意的是,我们发现这些贝飞达靶向的分类群的丰度与CXCR2配体基因的表达显著相关。我们的研究表明,口服贝飞达可通过干预脱硫弧菌属、黏液螺旋菌属、气味杆菌属、乳酸杆菌属与CXCR2信号之间的可能联系来改善小鼠的CAC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fff/5834773/4212b86f7508/CAS-109-666-g001.jpg

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