THE ONSET AND SEVERITY OF ULCERATIVE COLITIS IN IL-10 -/- MICE IS NOT DEPENDENT ON FECAL MICROBIOTA TRANSPLANTATION FROM ULCERATIVE COLITIS PATIENTS

Abstract

Abstract Inflammatory bowel disease (IBD) is a chronic inflammatory condition that affects around 1% of the U.S population. IBD is comprised of Chron’s Disease and Ulcerative Colitis (UC), with UC having a higher incidence rate. IBD is believed to be caused by immune dysfunction and several environmental factors. Specifically in UC, bacterial dysbiosis is positively correlated with colitis severity and incidence. Thus, we propose that genetically susceptible mice colonized with human colitis-associated bacteria will exhibit early onset and increased colitis severity compared to mice colonized with fecal microbiota from healthy individuals. To test this hypothesis, germ-free IL-10-/- mice of an average age of 20 weeks were gavaged orally with fecal samples from healthy individuals and a severe colitis patient with a fecal calprotectin level of 1947 ug/mg. The Disease Activity Index (DAI) was calculated based on occult blood, weight loss, stool consistency, and grimace. DAI was used to assess colitis severity weekly in transplanted mice for eight weeks.16S rRNA sequencing analysis showed a significant difference in alpha (Shannon Index) and beta diversity (unweighted UniFrac) between the colitis patient and healthy donors indicating dysbiosis (p=.0001; p=.001). The colitis donor had a reduction in species richness. Furthermore, recipient mice clustered with the donors in their bacterial composition. Compared to mice with healthy individual-associated bacteria, colitic-associated bacteria did not significantly increase the colitis incidence or severity in IL-10 -/- mice. Furthermore, there were no significant differences in DAI scores, organ weights, and gut permeability between the treatments. Thus, this study demonstrates that bacterial dysbiosis alone is not sufficient to induce colitis in genetically predisposed mice.