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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #338346

Research Project: Cancer Prevention via Diet

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: Diet- and genetically-induced obesity produces alterations in the microbiome, inflammation and Wnt pathway in the intestine of Apc+/1638N mice: comparisons and contrasts

Author
item Liu, Wei - University Of Massachusetts
item Crott, Jimmy - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Lyu, Lin - University Of Massachusetts
item Pfalzer, Anna - Vanderbilt University
item Li, Jinchao - University Of Massachusetts
item Choi, Sang-woon - Cha University
item Yang, Yingke - Hunan University Of Science And Technology
item Mason, Joel - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Liu, Zhenhua - University Of Massachusetts

Submitted to: Journal of Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/29/2016
Publication Date: 8/12/2016
Citation: Liu, W., Crott, J.W., Lyu, L., Pfalzer, A.C., Li, J., Choi, S., Yang, Y., Mason, J.B., Liu, Z. 2016. Diet- and genetically-induced obesity produces alterations in the microbiome, inflammation and Wnt pathway in the intestine of Apc+/1638N mice: comparisons and contrasts. Journal of Cancer. 7(13):1780-1790.

Interpretive Summary: Obesity is an established risk factor for colorectal cancer. In this study, we sought to understand the mechanism(s) by which obesity promotes colorectal by examining associations between gut microbiota, inflammation and a pro-tumorigenic pathway, the Wnt-signaling, in a genetically-engineered mouse model whose obesity was induced by one of two modalities, diet- or genetically-induced obesity. Our 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.

Technical Abstract: 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+/1638NLepr+/+ fed a low fat diet (10% fat), Apc+/1638NLepr+/+ fed a high fat diet (60% fat, diet-induced obesity), and Apc+/1638NLeprdb/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 (IFNgamma 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.