Lay Summary
Proposal No. IBD-0248R
Principal Investigator: Stephan J. Ott, M.D.
Applicant Organization: University-Hospital Schleswig-Holstein (Kiel, Germany)
Project Title: The gut flora under environmental aspects: metagenomic alterations of the intestinal microbiome associated with lifestyle and their role in the pathogenesis of inflammatory bowel diseases
Period of Award: January 1, 2009 - June 30, 2011
The contribution of environmental and microbiological factors to pathogenesis and etiology of inflammatory bowel disease (IBD) is still a matter of controversy. It appears very likely that alterations of lifestyle factors, which have risen during the last decades, have caused the dramatic increase of IBD in the western industrialized countries and the growing number of patients with IBD in the developing and threshold countries. The intestinal microflora is the mirror of these lifestyle factors and shows severe abnormalities in IBD patients. How far the intestinal microflora has changed over the last decades can be studied by comparing a microflora from a country with high incidence of IBD and countries with low incidence of IBD representing the “ancient” lifestyle of the pre-industrialization period.
To study the environmental factors effecting changes of the intestinal microflora, we are planning to collect microflora samples (by using intestinal mucosal biopsies during routine colonoscopy) from healthy individuals and IBD patients from three different countries: an urban region in Germany (a county with high numbers of IBD patients), and two rural regions of Lithuania and India (countries with still low, but growing incidence of IBD). The rural regions are characterized by not only the merely complete absence of IBD, but also by lifestyles (including diet, medical services, vaccines, etc.) corresponding to those decades ago. The individuals selected for this study will be carefully evaluated for environmental factors with a special attention to hygiene and dietary factors. The samples from all patients will be investigated by groups for the composition of the intestinal microflora, i.e., the relative number of bacterial species living in the gut. The human gut harbors 400-500 different bacteria and represents a very complex network of living microorganisms. Bacterial culture, as previously used for microbial studies, fails to describe the full amount of bacteria, since most (up to 90%) of bacteria are not cultivable. Therefore, we will employ modern genetic and molecular techniques to achieve a comprehensive description of the intestinal bacteria. The experimental techniques include Chip-technology and libraries of special genes of bacteria that can provide information about the composition and the nature of bacteria.
The aim of this study is to investigate the composition of intestinal bacteria/microbiota of individuals from regions with low incidence of IBD as compared to that of individuals of the western world with high incidence of IBD. The identification of such differences and the corresponding microbial factors could have important impact for IBD patients: one of the consequences of this study is the development of strategies to prevent IBD by elimination of possibly pathogenic environmental factors and to manipulate the intestinal flora towards the previous or former status decades ago.