VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer.

VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer.
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DOI:
10.1038/srep02868
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发表时间:
2013-10-08
期刊:
影响因子:
4.6
通讯作者:
Jobin, Christian
Jobin, Christian
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Arthur, Janelle C.;Gharaibeh, Raad Z.;Uronis, Joshua M.;Perez-Chanona, Ernesto;Sha, Wei;Tomkovich, Sarah;Muehlbauer, Marcus;Fodor, Anthony A.;Jobin, Christian

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虽然益生菌已被证明在预防实验性结肠炎相关性结直肠癌(CRC)方面取得了成功,但介入治疗的有益效果相对未知。在这里,我们表明,VSL#3益生菌的介入治疗改变了肠腔和粘膜贴壁的微生物区系,但不能预防偶氮甲烷/IL10−/−小鼠模型的结肠炎相关性结肠炎的炎症或肿瘤发生。与未治疗的小鼠相比,VSL#3(109CFU/动物/天)显著增强了肿瘤的穿透性、多样性、组织学不典型增生评分和腺癌侵袭性。Illumina 16S测序表明,VSL#3显著减少了(16倍)粘膜附着微生物区系中属于梭状芽胞杆菌属的细菌分类群的丰度。通过线性模型的中介分析表明,该分类单元是VSL#3喂养的小鼠肿瘤形成增加的一个贡献因素。我们得出结论,在AOM/IL10−/−模型中,VSL#3介入治疗可以改变微生物群落组成并增强肿瘤的发生。
Although probiotics have shown success in preventing the development of experimental colitis-associated colorectal cancer (CRC), beneficial effects of interventional treatment are relatively unknown. Here we show that interventional treatment with VSL#3 probiotic alters the luminal and mucosally-adherent microbiota, but does not protect against inflammation or tumorigenesis in the azoxymethane (AOM)/Il10−/− mouse model of colitis-associated CRC. VSL#3 (109 CFU/animal/day) significantly enhanced tumor penetrance, multiplicity, histologic dysplasia scores, and adenocarcinoma invasion relative to VSL#3-untreated mice. Illumina 16S sequencing demonstrated that VSL#3 significantly decreased (16-fold) the abundance of a bacterial taxon assigned to genus Clostridium in the mucosally-adherent microbiota. Mediation analysis by linear models suggested that this taxon was a contributing factor to increased tumorigenesis in VSL#3-fed mice. We conclude that VSL#3 interventional therapy can alter microbial community composition and enhance tumorigenesis in the AOM/Il10−/− model.
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