Our body provides an ideal ecosystem for microbial communities. The most complex and dense one, the gut microbiome, resides mainly in our lower intestine, and plays a fundamental role in host physiology and pathology.
To dissect these complex interactions, we focus on a set of representative species for the healthy human microbiome, synthetic, and human stool-derived communities, characterize them using automated high-throughput platforms and develop novel experimental set-ups to systematically study the microbiome-host interface, both in vitro and in vivo.
The research campus in Tübingen offers the ideal environment for our work at the cross-section between medical and biological research. We are part of the Cluster of Excellence “Controlling Microbes to Fight Infections”, which is dedicated to elucidate mechanisms governing competition and fitness within microbial communities and to develop targeted anti-infective strategies that promote microbiome integrity. In addition, we will join the highly interdisciplinary M3 Research Institute, which integrates tumor research (malignoma) with metabolism and microbiome research for a better understanding of how these systems mutually influence each other.
Medication has arisen as one of the most impactful factors on the gut microbiota composition and we identified a generalized effect of non-antibiotics on gut microbes (24% of the tested FDA-approved human-targeted drugs). For the vast majority of these drug-microbe interactions, we do not know the underlying drug targets in microbes and do not understand whether they have beneficial (required for the drug to work) or detrimental (side) effects for humans. In our lab, we want to further investigate questions at the drug-microbiome-host interface. Specifically, we aim at understanding how drugs can impact communities and whether one could use drugs to restore a healthy balance.
Microbial Colonization Dynamics
In the healthy gut, the microbiota generally provides “colonization resistance”, prohibiting the intrusion of new microbes into the community and protecting the host from enteropathogen infection. However, antibiotic-mediated microbiota perturbations disrupt this protective shield, resulting in infection, in particular with broadly antibiotic resistant nosocomial pathogens such as vancomycin-resistant Enterococcus faecium, Gram-negative Enterobacteriaceae and Clostridium difficile. Additionally, not only antibiotic therapy but also many other factors, such as certain diseases or dietary changes, can promote intestinal colonization with intruders. We want to understand the mechanisms underlying their colonization and long-term persistence in the community.
We aim at harnessing our understanding of drug-microbe and pathogen-commensal interactions in order to modulate the microbiome towards a balanced microbial community that prevents pathogen invasion and silences indigenous opportunistic pathogens (often referred to as pathobionts). Such microbiome modulation can be achieved by drugs with defined spectrum activity against specific microbes or microbial consortia. Alternatively, antagonistic drug interactions can be used to direct the spectrum of activity to a specific (sub-) group of bacteria. Since the microbiome composition is individual specific, so would be, at least to some degree, the solutions. Thus, the ultimate goal will be precision medicine strategies that will help to alleviate and cure microbiome-associated diseases.
The Microbiome-Host Interaction Laboratory receives generous funding from several funding agencies.
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