The Role of Lipocalin 2 in the Shaping of the Gastrointestinal Microbiota and Development of Inflammatory Bowel Disease in Mice

Abstract

The gastrointestinal microbiota have long been associated with health and disease in humans. Inflammatory bowel disease (IBD) is a disease thought to arise from a dysfunctional immune response to the commensal microbiota in the gut. The protein lipocalin 2 (LCN2) is a component of the innate immune response whose expression has shown to be upregulated during infection. It has also been found to limit bacterial growth by interfering with siderophore-mediated iron acquisition. Based on this knowledge it was hypothesized that LCN2 may play a role in the development of IBD by influencing the composition of the commensal microbiota and growth of pathogenic bacteria. In this project we study and compare the effect of LCN2 on the gastrointestinal microbiota and the development of colitis, one of the major types of IBD, in Lcn2 knock-out (KO) and wild-type (WT) mice. The mice were induced with colitis by administration of dextran sodium sulfate (DSS). Fingerprints of microbial communities found in stool samples collected before and during DSS treatment, as well as in faecal matter collected from the caecum and small intestine, were created by the use of 16S rRNA PCR coupled with denaturing gradient gel electrophoresis (DGGE). In addition, clinical features of colitis, such as weight loss, and histological alterations in the intestines were assessed.The study of the gastrointestinal microbiota revealed differences in the microbiota profiles between Lcn2 KO and WT mice. Significant differences were found both before the mice were induced with colitis and during the acute phase of colitis. As for the microbiota profiles during the chronic phase of colitis, no difference between the two genotypes could be observed, nor for the microbial profiles of the contents collected from the caecum and small intestine. The effect of habitation was also found to be a contributing factor to the shaping of the gastrointestinal microbiota throughout the experiment.In the study of LCN2 s influence on the development of colitis, no significant differences between Lcn2 KO and WT mice were found. Comparisons of clinical features and histological alterations in intestinal tissue revealed no significant difference between the two genotypes.