Modulating the gut microbiome composition with drugs

• Applicant: Professorin Dr. Lisa Maier
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409478429

A complex and diverse microbial community, referred to as the microbiome, colonizes the human gastrointestinal tract. This microbial ecosystem remains relatively stable during our adult life, providing us with a number of benefits– from immune training to increase of metabolic capacities. Yet, its composition is highly individualized. In recent years, the role of the gut microbiome on human health and disease has been extensively studied and a variety of environmental factors has been found to trigger intestinal microbial imbalances. Such imbalances increase susceptibility to infection and intestinal inflammation, and have been associated with a number of diseases, such as allergy and neurological disorders. While the strong impact of antibiotic intake on our microbiome has been long recognized, we have only recently begun to understand the full role of medication on our microbiome. During my postdoc, I led an effort on systematically mapping the effects of medication on gut microbes. Overall, we profiled >1000 drugs in 38 representative gut commensal species, revealing that at least a quarter of non-antibiotic drugs (> 200 drugs) impact the growth of gut microbes. These results corroborated the few association-based reports on medication effects on the gut microbiome of individuals, proving that these relationships are causal and triggered by direct inhibition of microbial growth. However, 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 my lab, I want to further investigate questions at the drug-microbiome-host interface, developing novel high-throughput in vitro experimental set-ups and validating promising observations in gnotobiotic mouse models. Specifically, I aim at assessing the stability of microbial communities, their resistance to intruders and their ability to keep in-check their pathogenic members. In addition, I propose to explore how drugs affect these processes and whether we can repurpose them to shift the microbiome towards desired compositions and healthy states. Similarly, I will identify drugs that deteriorate our microbiome compositions and thereby increase the risks for disease. My ultimate long-term goal is to improve our understanding of the complex gut microbial ecosystem and its role in health and disease. This will allow us to design intervention strategies for treating microbiome-related diseases, possibly tailored at an individualized level.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Anaerobic Chamber
• Instrumentation Group: 4670 Handschuhkästen, Schutzgasanlagen