Scientific Abstract
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
Epidemiological studies point to the critical role of environmental factors in the pathogenesis of chronic inflammatory barrier diseases, e.g., the chronic inflammatory bowel diseases (IBD) or asthma (“civilization diseases”). Lifestyle factors, such as nutrition, hygiene habits, and improved medical services, were accounted for the raising incidence of these disorders over the last decades in the industrialized countries (hygiene hypothesis). The intestinal microbiota as an integral part of the enteric mucosal barrier reflects the evolution of lifestyle factors. The aim of this study is to compare the composition of the intestinal microbiota of rural areas with low incidence of civilization diseases (representing the “ancient” lifestyle of the pre-industrialization period) and a region in an urban area, which is over decades influenced by multiple environmental factors (“modern” lifestyle). Healthy individuals and IBD patients from Germany, India, and Lithuania (n=90) will be recruited and investigated in groups (healthy vs. IBD, Lithuania vs. India vs. Germany). Biopsy material will be used as basic material to show alterations of the mucosa-associated microbiota as shown previously. State-of-the-art metagenomic techniques, such as large-scale 16S rDNA clone libraries and chip technology, which have enriched the repertoire of molecular microbiology in the description of complex ecosystems, will be employed to give a detailed description of the intestinal diversity in the different groups. In detail, large-scale pooled clone libraries with a total of more than 1.500 sequenced 16S rDNA and rRNA (cDNA) clones were generated for every group using broad-range universal primers as well as separate clone libraries for fungi (18S rDNA/RNA) and methanogens. A micro-array analysis for every single individual (spotted with target DNA of more than 400 intestinal bacteria, I-chip) is used to evaluate inter-individual differences. Modern statistical methods were employed to analyze and compare diversity and to estimate markers of the quality and appropriateness of clone libraries. The data will evaluate our previous hypothesis of dysbiosis with a loss of diversity and a shift of bacterial populations towards a more toxic profile (e.g., increase in diversity of Bacteroides sp.) as a pathogenetic principle in the growing incidence of modern chronic inflammatory disorders. On the other hand, the understanding of the behavior of complex microbial systems under environmental selection/pressure may open new ways in the (early in life) prevention and selective manipulation of the intestinal microbiota towards a general health improvement, e.g., by design of customized pre- or pro-biotic formulations or nutritional products. The presented study is therefore of special interest for IBD patients.