title: Diet- and Genetically-induced Obesity Produces Alterations in the Microbiome, Inflammation andWntPathway in the Intestine of Apc+/1638NMice: Comparisons and Contrasts.
abstract: Obesity is an established risk factor for colorectal cancer (CRC). Our previous study indicated that obesity increases activity of the pro-tumorigenicWnt-signaling. Presently, we sought to further advance our understanding of the mechanisms by which obesity promotes CRC by examining associations between microbiome, inflammation andWnt-signaling in Apc+/1638Nmice 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/dbfed 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 ofTuricibacterandDesulfovibriodecreased, butF. prausnitiziiincreased, in diet-induced obese mice (p < 0.05). In contrast, in genetically-induced obese mice,Bifidobacterium, A. muciniphila and E. rectaledecreased, butPeptostrptococcus,andE. coliincreased (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 theWnt-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 theWntpathway towards enhancing tumorigenesis.
authors.affiliation: Nutrition and Cancer Prevention Laboratory, School of Public Health and Health Sciences, University of Massachusetts, Amherst, USA.; Institute of Food Science and Technology, Shandong Academy of Agricultural Sciences, Jinan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, USA.
authors.forename: Jimmy W
authors.initials: JW
authors.lastname: Crott
authors.affiliation: Nutrition and Cancer Prevention Laboratory, School of Public Health and Health Sciences, University of Massachusetts, Amherst, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Lyu
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, USA.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pfalzer
authors.affiliation: Nutrition and Cancer Prevention Laboratory, School of Public Health and Health Sciences, University of Massachusetts, Amherst, USA.
authors.forename: Jinchao
authors.initials: J
authors.lastname: Li
authors.affiliation: Nutrition and Cancer Prevention Laboratory, School of Public Health and Health Sciences, University of Massachusetts, Amherst, USA.; CHA Cancer Research Center, CHA University, Seoul, Korea.
authors.forename: Sang-Woon
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Department of Molecular Medicine, Hunan University, Changsha, China.
authors.forename: Yingke
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, USA.; Tufts Medical Center Cancer Center, Tufts University, Boston, USA.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Mason
authors.affiliation: Nutrition and Cancer Prevention Laboratory, School of Public Health and Health Sciences, University of Massachusetts, Amherst, USA.; Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, USA.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Liu
keywords: Inflammation; Intestinal cancer.; Microbiome; Obesity; Wnt pathway