Diet- and Genetically-induced Obesity Produces Alterations in the Microbiome, Inflammation and Wnt Pathway in the Intestine of Apc(+/1638N) Mice: Comparisons and Contrasts

文献类型： 外文期刊

第一作者： Liu, Wei

作者： Liu, Wei;Lyu, Lin;Li, Jinchao;Choi, Sang-Woon;Liu, Zhenhua;Liu, Wei;Crott, Jimmy W.;Pfalzer, Anna C.;Mason, Joel B.;Liu, Zhenhua;Choi, Sang-Woon;Yang, Yingke;Mason, Joel B.

作者机构：

关键词： Obesity;Microbiome;Inflammation;Wnt pathway;Intestinal cancer

期刊名称：JOURNAL OF CANCER （ 影响因子：4.207； 五年影响因子：4.277 ）

ISSN： 1837-9664

年卷期： 2016 年 7 卷 13 期

页码：

收录情况： SCI

摘要： Obesity is an established risk factor for colorectal cancer (CRC). Our previous study indicated that obesity increases activity of the pro-tumorigenic Wnt-signaling. Presently, we sought to further advance our understanding of the mechanisms by which obesity promotes CRC by examining associations between microbiome, inflammation and Wnt-signaling in Apc(+/1638N) mice whose obesity was induced by one of two modalities, diet-or genetically-induced obesity. Three groups were employed: Apc(+/1638N)Lepr(+/+) fed a low fat diet (10% fat), Apc(+/1638N)Lepr(+/+) fed a high fat diet (60% fat, diet-induced obesity), and Apc(+/1638N)Lepr(db/db) fed a low fat diet (genetically-induced obesity). All animals received diets for 16 weeks from 8 to 24 weeks of age. The abundance of 19 bowel cancer-associated bacterial taxa were examined by real-time PCR. The abundance of Turicibacter and Desulfovibrio decreased, but F. prausnitizii increased, in diet-induced obese mice (p < 0.05). In contrast, in genetically-induced obese mice, Bifidobacterium, A. muciniphila and E. rectale decreased, but Peptostrptococcus, and E. coli increased (p < 0.05). Both diet-and genetically-induced obesity altered the expression of genes involved in bacterial recognition (MyD88) and increased inflammation as indicated by elevated levels of cytokines (IFN gamma and TNF-alpha for genetically-induced obesity, and IL-6 for diet-induced obesity). The elevated inflammation was associated with altered expression of genes that are integral components of the Wnt-signaling cascade in a fashion indicating its activation. These findings demonstrate that the composition of the small intestinal microbiome is affected differently in diet-and genetically-induced obesity, but both are associated with elevated intestinal inflammation and alterations of the Wnt pathway towards enhancing tumorigenesis.

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