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: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 2/1/2016
Publication Date: 4/1/2016
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 [abstract]. Federation of American Societies for Experimental Biology Conference, April 1-6, 2016, San Diego, California. 30:1166.4.

Interpretive Summary: Consumption of an obesigenic / high-fat (HF) diet is associated with an increase of inflammation-related colon cancer risk and may alter the gut microbiota. To test the hypothesis that a HF feeding accelerates inflammatory processes 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 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 these gut inflammation phenotypes, we also found that plasma IL6 and tumor necrosis factor 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 cell infiltration / molecular markers (e.g., iNOS), but also accompanies an increase of the Lachnospiraceae/Streptococcaceae in the hindgut of C57BL/6 mice.

Technical Abstract: Consumption of an obesigenic / high-fat (HF) diet is associated with an increase of inflammation-related colon cancer risk and may alter the gut microbiota. To test the hypothesis that a HF feeding accelerates inflammatory processes 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 inflammatory cell infiltration, inducible nitric oxide synthase (iNOS) protein concentration and cell proliferation marker (Ki67) in ileum and colon. Similarly, catenin expression was increased in colon (but not ileum). Consistent with these gut inflammation phenotypes, we also found that plasma IL6 and tumor necrosis factor 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 cell infiltration / molecular markers (e.g., iNOS), but also accompanies an increase of the Lachnospiraceae/Streptococcaceae in the hindgut of C57BL/6 mice.