Analysis of the intestinal lumen microbiota in an animal model of colorectal cancer.
Analysis of the intestinal lumen microbiota in an animal model of colorectal cancer.
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结直肠癌动物模型肠腔微生物群分析
DOI：
10.1371/journal.pone.0090849
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Qin H
中科院分区：
文献类型：
--
作者：
Zhu Q;Jin Z;Wu W;Gao R;Guo B;Gao Z;Yang Y;Qin H
近年来的研究表明，宿主遗传、环境和饮食等多种因素可促进健康粘膜向散发性结直肠癌的发展。越来越多的证据表明，肠道细菌与疾病的发生和发展有关。为了检查和分析肠道微生物群的组成，在没有混杂影响的情况下，我们建立了1,2 -二甲肼（DMH）诱导结肠癌的动物模型。利用该模型，我们在本研究中对16S rRNA基因V3区域进行焦磷酸测序，以确定肠道微生物物种的多样性和广度。我们的研究结果表明，肠道内的微生物组成在对照组和肿瘤组之间有显著差异。结直肠癌大鼠的管腔中厚壁菌门的丰度升高，而拟杆菌门和螺旋体的丰度降低。健康大鼠未检出梭杆菌，两组间观察到的变形菌种类比较，差异无统计学意义。有趣的是，变形杆菌在结直肠癌大鼠中的丰度更高。在属水平上，拟杆菌在结直肠癌大鼠中的丰度相对高于对照组（14.92%比9.22%,p<0.001）。健康大鼠中普雷沃菌（55.22%比26.19%）、乳酸杆菌（3.71%比2.32%）和密螺旋体（3.04%比2.43%）的丰度显著高于结直肠癌大鼠（p<0.001）。我们还证明了CRC大鼠肠道微生物群中产生丁酸盐的细菌如Roseburia和真细菌的显著减少。此外，肿瘤组中Desulfovibrio、丹毒杆菌科（erysipelotricaceae）和梭杆菌（Fusobacterium）也显著增加。在肿瘤组中，益生菌种类如瘤胃球菌和乳杆菌也同样减少。综上所述，我们可以得出健康大鼠与结直肠癌大鼠肠道菌群存在显著差异的结论。
Recent reports have suggested that multiple factors such as host genetics, environment and diet can promote the progression of healthy mucosa towards sporadic colorectal carcinoma. Accumulating evidence has additionally associated intestinal bacteria with disease initiation and progression. In order to examine and analyze the composition of gut microbiota in the absence of confounding influences, we have established an animal model of 1, 2-dimethylhydrazine (DMH)-induced colon cancer. Using this model, we have performed pyrosequencing of the V3 region of the 16S rRNA genes in this study to determine the diversity and breadth of the intestinal microbial species. Our findings indicate that the microbial composition of the intestinal lumen differs significantly between control and tumor groups. The abundance of Firmicutes was elevated whereas the abundance of Bacteroidetes and Spirochetes was reduced in the lumen of CRC rats. Fusobacteria was not detected in any of the healthy rats and there was no significant difference in observed Proteobacteria species when comparing the bacterial communities between our two groups. Interestingly, the abundance of Proteobacteria was higher in CRC rats. At the genus level, Bacteroides exhibited a relatively higher abundance in CRC rats compared to controls (14.92% vs. 9.22%, p<0.001). Meanwhile, Prevotella (55.22% vs. 26.19%), Lactobacillus (3.71% vs. 2.32%) and Treponema (3.04% vs. 2.43%), were found to be significantly more abundant in healthy rats than CRC rats (p<0.001, respectively). We also demonstrate a significant reduction of butyrate-producing bacteria such as Roseburia and Eubacterium in the gut microbiota of CRC rats. Furthermore, a significant increase in Desulfovibrio, Erysipelotrichaceae and Fusobacterium was also observed in the tumor group. A decrease in probiotic species such as Ruminococcus and Lactobacillus was likewise observed in the tumor group. Collectively, we can conclude that a significant difference in intestinal bacterial flora exists between healthy rats and CRC rats.
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