Cluster:

Metagenomics of the gut microbiota in enteric diseases

Coordinator:
  • Prof. Dr. Dr. Jürgen Heesemann, Max von Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, LMU München

Project Partners:
  • Prof. Dr. Ingo Autenrieth, Institut für medizinische Mikrobiolgie und Hygiene, Universitätsklinikum Tübingen
  • Prof. Dr. Julia-Stefanie Frick, Institut für medizinische Mikrobiolgie und Hygiene, Universitätsklinikum Tübingen
  • Prof. Dr. Daniel Huson, Zentrum für Bioinformatik, Universität Tübingen
  • Prof. Dr. Bärbel Stecher, Max von Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, LMU München

Description:
The gastrointestinal tract harbors a dense and complex microbial community that plays a major role in human health. In addition to its mainly beneficial functions the microbiota is also implicated in the etiology of chronic diseases (i.e. diabetes, metabolic syndrome, inflammatory bowel diseases/IBD). Furthermore, it takes a key modulating role the outcome of infectious diseases of the gastrointestinal tract. Due to the enormous complexity of the microbiota and the lack of appropriate analysis tools, little is known about the relative contribution of certain bacterial groups to these effects. Recent technological advancements of massively parallel DNA sequencing technologies have enabled the fast and inexpensive phylogenetic analysis of microbial communities as well as enabled the analysis of the entire microbiome (= total genetic information of the microbiota of a given composition).

In particular, it is unclear to date, how inflammatory immune responses modify microbiota structure and composition, though it has been shown that inflammation affects gut microbial ecology and leads i.e. to overgrowth of pathogens and specific types of commensal bacteria (i.e. Enterobacteriaceae). The mechanisms driving these microbiota alterations as well as their consequences for the host (IBD pathogenesis, clearance of enteric pathogens) have not been investigated in detail. We will use state of the art deep sequencing approaches for phylogenetic microbiota profiling and microbiome analysis in different types of preclinical mouse models for IBD and enteric infections.

We aim at identifying parts of the microbiota involved in murine IBD pathogenesis, analyzing inflammation-induced microbiota changes in the course of IBD development using gnotobiotic and conventional animal models. We aim at elucidating the role of the gut microbiota in the outcome of infection with enteropathogenic Yersinia spp. and Salmonella spp. strains. The goal is to define metagenomic signatures of the inflammatory microbiome.

Our work will form the basis of mechanistic analyses of host and bacterial factors involved in the three-way interaction of the host´s immune system, the microbiota and enteric pathogens. Eventually, this may lead to improvement of diagnosis and therapeutic intervention of human infectious diseases and IBD.


 
The host, the microbiota and enteric pathogens:
A complex interplay of three partners. Inflammatory mucosal immune responses can lead to microbiota shifts which in turn may contribute to the pathogenesis of inflammatory disease of the intestine.


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