Scientific Abstract
Proposal No. IBD-0225R3
Principal Investigator: Salvatore Cucchiara, M.D., Ph.D.
Applicant Organization: University of Rome “La Sapienza” (Italy)
Project Title: Molecular characterization of mucosa-associated intestinal microbiota and intestinal innate immune response: searching for additional mechanisms in pediatric Crohn’s disease
Period of Award: March 1, 2009 – February 28, 2011
The aims of our study are: to compare the qualitative compositions of the mucosa-associated microbiota in different phases of disease (acute and remission) and in different topographic gut localization (ileum, colon and rectum), to asses a putative pathological role of qualitative dysbiosis; to quantify and to characterize mucosa-associated aerobic and facultative anaerobic bacteria to assess if a particular subset of E. coli strains could be associated to CD; to screen E.Coli strains genes for genes associated with pathogenicity; to investigate adhesive/invasive properties of isolated E.coli strains by analyzing their adhesion to intestinal cell lines; to investigate the link between the innate immune response to adhesive/invasive bacteria and the development of intestinal inflammation.
This study is innovative because there is emerging evidence that the intestinal mucosa of CD patients is abnormally colonized by bacteria species, among which E. coli with specific adherent, invasive and survival features predominate; however, at present, very little is known about their identification, concentration, localization and, finally, their interaction with specific immunology cell repertoire. Furthermore, the study is innovative because it deals with a pediatric population with IBD. This aspect is of great relevance due to the recently increased interest of the scientific community for the IBD occurring in childhood. Indeed, a rise in the incidence of CD in pediatric age has been shown and there is a growing view that the pediatric CD is not just the adult disease in “little people”, but a condition with specificities and peculiarities related to the genetics, pathogenesis, phenotypes, therapy and clinical course. At a preliminary stage, the project is aimed at defining whether the presence of bacterial sub-set can be correlated to IBD. Thereafter, the selected strains will be used to investigate the interaction between microbiota and main receptors of the innate immune response. By revealing and characterizing new steps in the inflammatory cascade leading to intestinal inflammation, the results obtained project might also provide new clues for novel therapeutic approaches in pediatric CD.