The Impact of a Naturalized Environment and Dietary Fiber on DSS-Induced Low-Grade Colonic Inflammation in Mice

Abstract

Background: Inflammatory bowel disease (IBD) is a growing problem worldwide, especially in Western countries. Mouse models have been useful in understanding such diseases, but differences exist between the immunophenotype of conventional laboratory mice and wild-living mice. Moreover, fiber intake has decreased in Western countries the last decades, which has been associated with increased risk of several diseases including IBD and cancer. To improve the translation potential to humans, there is a need to create mouse models that mimic the diversity of human environments and diets by producing a more realistic setting in the lab.

Aims: We wanted to investigate the potential effects of a naturalized environment and a fiber-rich diet on DSS-induced colonic inflammation in mice by looking at disease development, nuclear factor kappa B (NF-kB) activity in colon, gene expression of barrier- and immuno-related genes in mucosa, and levels of the inflammation biomarker lipocalin-2 (LCN-2) in feces.

Methods: 64 C57BL/6JRj were housed in environments typical for a clean laboratory or in a farmyard-like habitat (“feralized mice”). They received a fiber-rich (FR) or fiber-low (FL) diet and were weighed every other week. After five weeks the experimental mice were given dextran sulfate sodium (DSS) to induced low-grade inflammation. After a recovery period the same mice went through a new cycle of DSS administration, followed by euthanasia. Different organs were dissected out including colon that were measured and scraped for mucosa content. RNA was extracted from these samples and analyzed by real-time quantitative PCR using Biomark™ HD. In vivo and ex vivo imaging was performed to measure NF-kB activity, and fecal LCN-2 levels were measured by sandwich ELISA.

Results: The results showed that DSS affected all groups, leading to inflammation in the colon, especially the FR Lab group. This group had highest disease severity and weight loss, which was reflected in the expression of several genes connected to mucus, immunosurveillance, and inflammation, in addition to fecal LCN-2 levels. The feralized groups had low disease severity and body weight loss, and lower expression of genes related to mucus and immunosurveillance than their non-DSS-treated control groups.

Conclusion: A definite conclusion is difficult to draw, but based on disease score, gene expression, and LCN-2 amounts it appears that feralization has a positive health effect on DSS-induced low-grade inflammation in colon. Surprisingly, a combination between a clean environment and a FR diet seems to adverse the effects of DSS treatment, reflected in several of the parameters measured.