Altered Interactions between the Gut Microbiome and Colonic Mucosa Precede Polyposis in APCMin/+ Mice.
Altered Interactions between the Gut Microbiome and Colonic Mucosa Precede Polyposis in APCMin/+ Mice.
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DOI：
10.1371/journal.pone.0127985
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Li E
中科院分区：
文献类型：
--
作者：
Son JS;Khair S;Pettet DW 3rd;Ouyang N;Tian X;Zhang Y;Zhu W;Mackenzie GG;Robertson CE;Ir D;Frank DN;Rigas B;Li E
腺瘤性结肠息肉病（APC 基因）突变是腺瘤-癌序列中的一个早期事件，存在于 70-80% 的散发性人类结直肠腺瘤和癌中。为了检验 APC 基因突变在息肉病发生之前改变微生物与宿主肠粘膜相互作用的假设，使用不依赖培养的方法（靶向 qPCR 检测和 16S rRNA 基因 V1V2 高变区的 Illumina 测序）比较 30 只六周龄 C57BL/6 APCMin/+ 和 30 只同源野生型 (WT) 小鼠的肠道微生物组成。结果表明，与患有肠肿瘤的 12-14 周龄 APCMin/+ 小鼠类似，未检测到肿瘤的 6 周龄 APCMin/+ 小鼠表现出结肠中拟杆菌属的相对丰度增加。对近端结肠 RNA 样本子集（6 APCMin/+，6 WT）进行的平行小鼠 RNA 序列分析揭示了 130 个差异表达基因（DEG，倍数变化 ≥ 2，FDR <0.05）。通过使用1-r相异性测量对DEG进行层次聚类，其中r代表Pearson相关性和Ward最小方差联动，以减少输入变量的数量。当簇质心（中位数）与 APC 基因型一起作为负二项式 (NB) 回归模型的输入变量时，除了 APC 基因型外，七个小鼠基因簇中的四个与拟杆菌属相对丰度的增加显着相关。四个簇中的三个包含编码免疫球蛋白可变区和非蛋白质编码 RNA 的几个下调基因。这些结果支持这样的观点：APC 基因突变会改变息肉病之前的结肠-微生物相互作用。目前尚不清楚针对改善 APCMin/+ 小鼠生态失调的干预措施（例如通过益生菌、益生元或抗生素）是否可以减少肿瘤形成。
Mutation of the adenomatous polyposis coli (APC gene), an early event in the adenoma-carcinoma sequence, is present in 70-80% of sporadic human colorectal adenomas and carcinomas. To test the hypothesis that mutation of the APC gene alters microbial interactions with host intestinal mucosa prior to the development of polyposis, culture-independent methods (targeted qPCR assays and Illumina sequencing of the 16S rRNA gene V1V2 hypervariable region) were used to compare the intestinal microbial composition of 30 six-week old C57BL/6 APCMin/+ and 30 congenic wild type (WT) mice. The results demonstrate that similar to 12-14 week old APCMin/+ mice with intestinal neoplasia, 6 week old APCMin/+ mice with no detectable neoplasia, exhibit an increased relative abundance of Bacteroidetes spp in the colon. Parallel mouse RNA sequence analysis, conducted on a subset of proximal colonic RNA samples (6 APCMin/+, 6 WT) revealed 130 differentially expressed genes (DEGs, fold change ≥ 2, FDR <0.05). Hierarchical clustering of the DEGs was carried out by using 1-r dissimilarity measurement, where r stands for the Pearson correlation, and Ward minimum variance linkage, in order to reduce the number of input variables. When the cluster centroids (medians) were included along with APC genotype as input variables in a negative binomial (NB) regression model, four of seven mouse gene clusters, in addition to APC genotype, were significantly associated with the increased relative abundance of Bacteroidetes spp. Three of the four clusters include several downregulated genes encoding immunoglobulin variable regions and non-protein coding RNAs. These results support the concept that mutation of the APC gene alters colonic-microbial interactions prior to polyposis. It remains to be determined whether interventions directed at ameliorating dysbiosis in APCMin/+mice, such as through probiotics, prebiotics or antibiotics, could reduce tumor formation.
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影响因子：
3.7
作者：
Chen W;Liu F;Ling Z;Tong X;Xiang C
通讯作者：
Xiang C
影响因子：
64.5
作者：
GRODEN, J;THLIVERIS, A;WHITE, R
通讯作者：
WHITE, R
影响因子：
56.9
作者：
Markle, Janet G. M.;Frank, Daniel N.;Danska, Jayne S.
通讯作者：
Danska, Jayne S.
影响因子：
3.7
作者：
Gu S;Chen D;Zhang JN;Lv X;Wang K;Duan LP;Nie Y;Wu XL
通讯作者：
Wu XL
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y