Acute high fat diet disrupts intestinal barrier repair

Abstract

Abstract Over-consumption of high fat diets (HFD) corresponds to increased incidence and severity of many chronic inflammatory diseases, including those of the intestinal tract. The impact of HFD feeding on bodily tissues has largely been studied in the context of obesity. Long-term exposure to HFD has been shown to decrease barrier function, allowing for bacterial penetration into the body resulting in chronic inflammation. However, this effect is secondary to adipose tissue dysfunction making it difficult to determine the direct impact of HFD on intestinal barrier function. The intestine acts as a protective barrier and our immune system supports the proper functioning of this barrier, aiding in protection from pathogens. Sustained damage or loss of proper barrier function can result in chronic inflammation and diseases such as inflammatory bowel disease (IBD). We hypothesized that intestinal exposure to HFD would directly alter the intestinal barrier resulting in enhanced inflammation. To test this, we utilized short-term HFD feeding in the context of mouse models of colitis. Our data demonstrates that HFD increases susceptibility to colitis with increased weightloss, aberrant epithelial cell proliferation, loss of goblet cells and the mucus layer necessary to prevent microbial penetration into the body. We also identified dysregulated immune responses resulting in an inability of intestinal immune cells to properly support barrier function and repair. Together, we find that HFD feeding directly promotes altered functions of intestinal epithelial and immune cells leading to a barrier repair defect resulting in an inability to repair epithelial damage and increasing pathology in models of IBD.