Colonic inflammation and enhanced-beta-catenin signaling accompany an increase of the Lachnospiraceae/Streptococcaceae in the hind gut of high-fat diet-fed mice

Authors: Zeng, Huawei; ISHAQ, SUZANNE - University Of Vermont; ZHAO, FENG-QI - University Of Vermont; WRIGHT, ANDRE-DENIS - University Of Arizona

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/26/2016
Publication Date: 9/1/2016
Publication URL: https://handle.nal.usda.gov/10113/5302156
Citation: Zeng, H., Ishaq, S.L., Zhao, F., Wright, A.G. 2016. Colonic inflammation and enhanced-beta-catenin signaling accompany an increase of the Lachnospiraceae/Streptococcaceae in the hind gut of high-fat diet-fed mice. Journal of Nutritional Biochemistry. (35)30-36.

Interpretive Summary: The incidence of inflammatory bowel disease (IBD) is rising in the Western world. The precise cause of IBD is unknown, and the spread of the “Western” diet, high in fat has been demonstrated as a promoting effect of a high-fat diet (HFD) on the risk of IBD. In addition, it is known that consumption of a HFD can lead to accumulation of excess body fat that is associated with adipose tissue dysfunction and a chronic state of low-grade inflammation. However, little is known about the comparative effect of a HFD on inflammation between ileum and colon segments, and the association of gut bacterial composition. In this study, we demonstrate that HFD increased not only inflammatory status in both ileum and colon but also beta-catenin (colon cancer risk signaling) expression in colon, which is accompanied by an increase of Lachnospiraceae and Streptococcaceae bacteria in the gut in our mouse model. These data provide novel insights into the obesity-related IBD, and will be useful for scientists who are interested in the prevention of obesity-related IBD and colon cancer.

Technical Abstract: Consumption of an obesigenic / high-fat (HF) diet is associated with a high colon cancer risk, and may alter the gut microbiota. To test the hypothesis that a HF feeding accelerates inflammatory process and changes gut microbiome composition, C57BL/6 mice were fed a HF (45% energy) or low-fat (LF) (10% energy) diet for 36 weeks. At the end of the study, body weights in the HF group were 35% greater than those in the LF group. These changes were associated with dramatic increases in body fat composition, inflammatory cell infiltration, inducible nitric oxide synthase (iNOS) protein concentration and cell proliferation marker (Ki67) in ileum and colon. Similarly, beta-catenin expression was increased in colon (but not ileum). Consistent with gut inflammation phenotype, we also found that plasma leptin, IL6, and tumor necrosis factor-alpha concentrations were also elevated in mice fed the HF diet, indicative of chronic inflammation. Fecal DNA was extracted and the V1-V3 hypervariable region of the microbial 16S rRNA gene amplified using primers suitable for 454-pyrosequencing. Compared to the LH group, the HF group had high proportions of bacteria from the phylum Firmicutes, especially the family Lachnospiraceae which is known to be involved in the development of metabolic disorders, diabetes and obesity. Taken together, long-term HF consumption not only increases inflammatory cytokines, histological status, '-catenin and related cell signaling, but also accompanies an increase of the Lachnospiraceae/Streptococcaceae in the hindgut of C57BL/6 mice.