Abstract
BACKGROUND AND AIMS: Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis (UC), are inflammatory gastrointestinal conditions in which the pathogenesis is influenced by immune dysfunction, genetics, and environmental factors. Of the 2 conditions, UC is more prevalent, and there is a positive correlation between bacterial dysbiosis and colitis severity and incidence. Therefore, we hypothesize that mice that are genetically predisposed to colitis when colonized with colitic associated bacteria will exhibit an early onset of colitis biomarkers. METHODS: Four sets of germ-free interleukin-10 -/- mice were gavaged orally with pooled fecal samples from 2 healthy individuals or an individual with severe colitis or healthy mice or dextran sodium sulfate (DSS)-induced colitis mice. The disease activity index was used to rank colitis severity weekly in transplanted mice for eight weeks. RESULTS: There were significant differences in alpha (Shannon Index) and beta diversity (Bray-Curtis) between healthy and colitic-associated microbiota recipients, indicating dysbiosis (human fecal microbial transplantation P = 8.09∗10(-6), P = .001); (Mice fecal microbiota transplant P = .0197, P = .025). Despite the lack of colitis development, UC-associated microbiota recipients had reduced mucus thickness and increased expression of proinflammatory cytokines in the distal colon compared to healthy-associated microbiota recipients. However, DSS-induced colitis associated microbiota recipients did not show an increase in colitis biomarkers compared to healthy associated microbiota recipients. CONCLUSION: This study demonstrates that UC-associated bacterial dysbiosis induces colonic inflammation and mucus thinning, biomarkers of early colitis onset, in interleukin-10 -/- mice compared to mice with healthy human associated bacteria.Colitis induction depends on bacterial community stability as DSS-induced colitis associated microbiota recipients did not show an increase in colitis or colitis biomarkers in the absence of DSS.