High fat diet alters gut microbiota and the expression of Paneth cell-antimicrobial peptides preceding changes of circulating inflammatory cytokines

Authors: GUO, ZIULAN - University Of Massachusetts; LI, JINCHAO - University Of Massachusetts; TANG, TENYONG - University Of Massachusetts; Zeng, Huawei; WOOD, RICHARD - University Of Massachusetts; LIU, ZHENHUA - University Of Massachusetts

Submitted to: Mediators of Inflammation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/30/2017
Publication Date: 2/27/2017
Publication URL: https://handle.nal.usda.gov/10113/5832858
Citation: Guo, Z., Li, J., Tang, T., Zeng, H., Wood, R., Liu, Z. 2017. High fat diet alters gut microbiota and the expression of Paneth cell-antimicrobial peptides preceding changes of circulating inflammatory cytokines. Mediators of Inflammation. doi:10.1155/2017/9474896.

Interpretive Summary: Obesity is established as a critical risk factor for many diseases including colorectal cancer. A large body of evidence has demonstrated that an increased adiposity leads to a chronic low-grade activation of inflammatory processes that are related to changes in the gut microbial environment. However, it remains to be defined whether the alteration in gut bacteria results directly from the diet or from the altered intestinal microenvironment in an obese state. We addressed this question in a diet-induced obesity animal model in which animals were fed obesity-inducing diets for increasing times. We found that an obesity causing diet first alters gut bacterial composition prior to intestinal inflammation. Therefore, our results suggest that the change of gut bacteria, may play a major role in promoting intestinal inflammation in an obese state at the early stage. These data provide novel insights into the obesity-related gut inflammation and will be useful for scientists who are interested in the prevention of obesity-related colon cancer.

Technical Abstract: Obesity is established as a critical risk factor for many diseases including intestinal cancer. One of the responsible mechanisms for this relationship is the chronic inflammation driven by obesity. However, it remains to be defined whether high fat diet-induced obesity first exacerbates the intestinal inflammatory status by circulating cytokines produced by adipose tissue, and thereafter alters gut microbiota; or the high fat diet first alters the gut microbiota, and then drives intestinal inflammation. To address this question, we fed male C57BL/6 mice with a high fat diet (HF, 60%) and sacrificed sequentially after 8, 12, 16 weeks, and then composition of gut microbiota and expressions of antimicrobial peptides were determined. Gut microbiota was altered starting at 8-wk HF feeding, with a higher abundance of Firmicutes and Lactobacillus, and a lower level of Bacteroidetes, Bacteroides, Prevotella, Bifidobacteria and Turicibacter (p < 0.05) compared to the control animals fed with a low fat diet (LF, 10%). Animals with 12- and 16-wk HF feeding have significantly reduced Paneth antimicrobial peptides lysozyme and RegIII-gamma (p < 0.05). These alterations preceded the significant elevations of circulating inflammatory cytokines IFN-gamma and TNF-alpha, which were observed until feeding a HF diet for 16 weeks (p < 0.05). Our data demonstrated that HF induced alterations of gut microbiota accompanying with decreased expression of Paneth cell-antimicrobial peptides, but preceding the elevation of circulating inflammatory cytokines. These results indicated that high fat diet may induce intestinal inflammation via altering gut microbiota, and it occurs prior to the potential influence by circulating inflammatory cytokines.