Work

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

Year: 2016

Type: article

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 +/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 (IFNγ and TNF-α 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.

Source: Journal of Cancer

DOI: 10.7150/jca.15792