1.1 Microbe-host-interactions in health and diseaseMicroorganisms populate all environmentally exposed surfaces on the human and animal body. Hereby the location-specific microbial ecosystem develops in response to prevailing biological and physiochemical properties of the respective environment.1, 2 The gastrointestinal tract harbours a high number of taxonomically diverse microorganisms. Due to very close proximity to the richest immune-structure of the host, the intestinal ecosystem is of crucial importance to prime microbe-host interaction in a homeostatic immune-situation. The totality of these organisms – including bacteria, viruses, archaea and eukaryotes (yeasts, protozoa) and their genes – represents the “intestinal microbiome”. The most abundant microorganisms in the human and murine intestine are bacteria of the phyla Bacteroidetes and Firmicutes; followed by Proteobacteria, Actinobacteria, Verrucomicrobia, Tenericutes and Fusobacteria.3, 4 At lower taxonomic levels, the diversity is very high, with approximately 150-200 dominant bacterial species per individual.5 However, great inter-individual differences were observed in the overall microbial community.6, 7 The recently described high intra-species variation at strain level puts even more emphasis on this high diversity.8 Large-scale sequencing studies like the European MetaHIT project and the US Human Microbiome Project (HMP), confirmed this great inter-individual variability in the overall bacterial composition.9 Results from the HMP also showed that despite compositional variance, great redundancy of metabolic pathways are found, which seem equally distributed along all intestinal samples. This highlights that it is virtually impossible to clearly define a “healthy” microbiota solely based on evaluation of relative abundance of different gut inhabitants.1.1.1 Disruption of microbe-host-interaction in inflammatory bowel diseasesDue to the close proximity to the host´s largest immune structure, the intestinal microbiota gains centre stage for development of Crohn’s disease (CD) and ulcerative colitis (UC), the two main forms of inflammatory bowel diseases (IBD). While inflammation in CD patients mainly occurs in the terminal ileum and is found in the proximal colon only occasionally, inflammation in UC is confined to the colon.10, 11 The aetiology of IBD is not yet fully known, however, an over reactive mucosal immune system responding upon commensal stimuli is regarded as reason for pathology onset.12, 13 This hypothesis was supported by the observation of delayed recurrence of ileitis after faecal stream diversion in CD patients.14 Furthermore, genome-wide association studies identified genes involved in microbial signaling, underlining the role of gut microbes in IBD pathogenesis. At present, more than 200 genetic polymorphisms were identified, and there are more to come.15-17 However, disease concordance in identical twin studies explains only up to 40% of CD risk, leading to the general agreement that environmental factors (in their sum regarded as the “exposome”) dominate IBD risk and development. Epidemiologic studies showed higher IBD prevalence in industrialized countries and adoption of higher incidence rates in the second generation of immigrants, hinting to the fact that adoption of lifestyle (most likely diet) may be a risk factor for later IBD development.18-20 Genetic predispositions and inflammation were shown to be accompanied by altered composition and metabolic activity of intestinal microbial communities. This alteration in microbial composition that was associated with pathology, was defined as “dysbiosis”.21-26 In coexistence with genetic susceptibility to IBD, the microbiota is assumed to be causative for disease development, “…but whether the changes are causal or secondary to inflammation remains uncertain.”27Also other pathologies like obesity, diabetes, cardiovascular disease and even depression or multiple sclerosis have been recently connected to intestinal dysbiosis.24, 28-34 However, the proof of a clear causative relation is still missing. Furthermore, those pathologies are quite diverse, therefore common physiognomies of dysbiosic ecosystems are difficult to define.