Improving Animal Models and Investigating a Raspberry-Derived Treatment for Leaky Gut Diseases

Abstract

The intestinal epithelium is a selective mass transport barrier where nutrients from our food are absorbed into the bloodstream while bacteria and other pathogens remain in the intestine. When intestinal barrier function is diminished pathogens can cross the epithelium, initiating a chronic cycle of immune responses. A growing portion of the population has intestinal barrier dysfunction, commonly called a leaky gut. This leaky gut is implicated in diseases such as inflammatory bowel disease, but we lack an understanding of how the disease manifests or how to treat it most effectively. This work focuses on improving the animal modelsused to study inflammatory bowel disease and introduces an innovative, fruit-derived approach to treating leaky gut diseases. The DSS colitis animal model is the most commonly used inflammatory bowel disease model, but the typical administration procedures result in rapid and severe colitis. This leads to symptoms, including increased intestinal permeability, that are more severe than those found inclinical cases. Because this animal model is used in a wide variety of applications to study inflammatory bowel disease, it is important to understand how to better implement it to produce more disease-relevant symptoms. We developed an attenuated DSS model that still produces the hallmarks of chemically induced colitis, but results in intestinal permeability increases that better recapitulate what occurs in patients. We also demonstrate methods for reducing variability when administering DSS, which increases usability of the model and reduces the need for repeat experiments.To address the growing need for inflammatory bowel disease treatments, we examined how fruits and vegetables affect intestinal permeability. Fruits and vegetables are rich inpotentially active natural products, and these metabolites are generally well-handled by the intestine. We show that raspberry reduces intestinal permeability in vitro and in vivo, which could offer patients an option for disease treatment and prevention. Because this treatment is derived from raspberry, it should not be associated with any of the undesirable side effects of traditional inflammatory bowel disease treatments, improving patient compliance and quality of life. This could offer a safe therapeutic approach for treating inflammatory bowel disease by directly targeting one of the suspected causes: increased intestinal permeability.