- MIMIC -Culture-based and molecular study of the mouse gut microbiometowards Minimal Microbial Consortia

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The gut microbiota is very important for mammalian host physiology. It is thus crucial to put effort into understanding its structure and functions. Omics technologies have generated major breakthroughs in microbiome research, but they only show correlations. To test causal relationships and to study molecular mechanisms, mouse models, have been extensively used in many research projects worldwide and within SPP 1656. However, there is an obvious deficit of bacterial strains and genomes from the mouse gut microbiome (only 12 strains are available to date from culture collections), because emphasis has been put on molecular studies over the last decade. This is a major limitation for annotation of omics datasets and for colonization studies in germfree mice to test causal effects of microbiomes known to have specific features depending on their host species of origin. To overcome these limitations, the present central project MIMIC aims at improving preliminary work performed during phase 1 of SPP 1656 on the isolation and description of mouse gut bacteria to deliver a unique and well-curated strain collection. The collection will give researchers easy access to bacterial strains and corresponding genomic information, but most of all will serve as a foundation to implement a new bioinformatics tool (MIMIC) for automated design of minimal microbial consortia adapted to individual experimental designs in mouse models of interest. The design of minimal consortia will be based on metagenomic coverage strategies and will be embedded into the newly established bioinformatic platform IMNGS for dissemination (www.imngs.org). Considering known phenotype variability between mouse facilities, an innovative approach that allows generation of customized minimal consortia of bacteria based on the cultivable fraction of native ecosystems is highly relevant regarding standardization of mouse models and mechanistic understanding of bacteria-bacteria and bacteria-host interactions. The MIMIC project is a perfect match to current needs in the field and within SPP 1656. It is embedded in the consortium activities via multiple interactions with partners, e.g., to obtain materials from different facilities for isolation of bacteria, to gain access to already isolated strains that require proper description, and to generate minimal consortia adapted to current needs within SPP 1656. In summary, the present MIMIC proposal is a unique opportunity to use complementarity culture-based and molecular approaches to discover novel bacterial diversity and to create and deliver useful resources to the priority program and more generally to the scientific community. Funding by the DFG will allow putting preliminary activities on a solid basis and integrating an internationally recognized bioresource center (the DSMZ) to SPP activities on microbe-host interactions.