Drug-Microbiome-Host-Interactions

The  long-term research goal is to gain a detailed and comprehensive understanding of the role of the gut microbiota in health and disease. 

In recent years, we have developed a particular interest in the effects of medicinal drugs on the human gut microbiome. To understand the interactions between small molecules, the microbiome and the host, thelab uses microbiology-driven and cultivation-based bottom-up approaches. As a starting point, the team systematically maps the direct effects of drugs on gut bacteria in pure cultures, in microbial communities and in vivo. Based on the results of these systematic approaches, the team elucidates the underlying molecular mechanisms, investigates the development of resistance and explores the consequences for the host, such as drug efficacy, toxicity, pathogen colonisation or side effects. The current focus is on anticancer and psychotropic drugs, as these therapeutic drug classes show strong direct effects on the gut microbiome.

We are further using our insights into how small molecules modulate the gut microbiome to develop strategies for targeted pathogen decolonisation. For example, the lab aims to reverse ectopic colonisation of the gut with species from the oropharyngeal cavity - a scenario that has been shown to cause enteric environmental dysfunction (EED), is associated with chronic malnutrition in children and linked to colorectal cancer. 

In addition, the lab is developing methods and protocols for isolating, culturing and investigating previously under-studied members of the human microbiome. This includes developing tools to illuminate the genomic dark matter of the human gut microbiome.

Wissenschaftliche Abbildung
Research in the Maier lab focuses on the interactions between drugs and the gut microbiome, including the consequences for the host.

Lisa Maier is a biochemist by training and received her doctorate in 2014 from ETH Zurich, Switzerland. During her PhD in the lab of Prof. Wolf-Dietrich Hardt, she investigated the role of the microbiome in Salmonella infections. As part of the interdisciplinary postdoctoral program at EMBL in Heidelberg, she worked with Dr. Athanasios Typas and Dr. Kiran Patil on high-throughput methods for the systematic investigation of drug-microbiome interactions. In 2019, supported by the Emmy Noether Program of the German Research Foundation, she established her independent research group at the Interfaculty Institute of Microbiology and Infection Medicine Tübingen. In 2022, she was awarded a Starting Grant from the European Research Council and accepted a call to a full professorship at the Medical Faculty of the University of Tübingen. Her lab is integrated into the Cluster of Excellence "Controlling Microbes to Fight Infections" and the interdisciplinary M3 (Malignoma-Metabolome-Microbiome) Research Institute in Tübingen.

  • Excellence Cluster ‘Controlling Microbes to Fight Infections’ (CMFI), University of Tübingen, Germany

  • Interfaculty Institute of Microbiology & Infection Medicine Tübingen (IMIT), University of Tübingen, Germany

  • Institute of Medical Microbiology and Hygiene, University Hospital Tübingen, Germany

  • German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany

map
the direct effects of drugs on gut bacteria
genomic
dark matter of the human gut microbiome
EED
enteric environmental dysfunction

Technology platform

Our high-throughput culturomics and screening systems allow us to analyse diverse anaerobic bacteria from multiple phylogenies under thousands of conditions. These conditions include different growth media and a range of stressors from molecular to environmental. 

We employ highly efficient parallel testing methods using simple yet reliable assays in multi-well plates, such as quantitative growth assessments or assays based on fluorescence and chemiluminescence readouts.

Our test protocols cover a wide range of setups, from bacterial monocultures to complex microbial communities of human-associated microbiomes. We also work with synthetic communities that mimic microbiome compositions associated with specific disease states.

Laborausstattung

Selected publications

  • Maier L, Goemans CV, Wirbel J, et al. Unravelling the collateral damage of antibiotics on gut bacteria. Nature. 2021;599(7883):120-124. doi:10.1038/s41586-021-03986-2
  • Zimmermann M, Patil KR, Typas A, Maier L. Towards a mechanistic understanding of reciprocal drug-microbiome interactions. Mol Syst Biol. 2021;17(3):e10116. doi:10.15252/msb.202010116
  • Klünemann M, Andrejev S, Blasche S,…, Maier L, et al. Bioaccumulation of therapeutic drugs by human gut bacteria. Nature. 2021;597(7877):533-538. doi:10.1038/s41586-021-03891-8
  • Wotzka SY, Kreuzer M, Maier L, et al. Escherichia coli limits Salmonella Typhimurium infections after diet shifts and fat-mediated microbiota perturbation in mice. Nat Microbiol. 2019;4(12):2164-2174. doi:10.1038/s41564-019-0568-5
  • Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555(7698):623-628. doi:10.1038/nature25979
  • Wilck N, Matus MG, Kearney SM, …, Maier L, et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature. 2017;551(7682):585-589. doi:10.1038/nature24628
  • Maier L, Diard M, Sellin ME, et al. Granulocytes Impose a Tight Bottleneck upon the Gut Luminal Pathogen Population during Salmonella Typhimurium Colitis. Luo ZQ, ed. PLoS Pathog. 2014;10(12):e1004557. doi:10.1371/journal.ppat.1004557
  • Maier L, Vyas R, Cordova CD, et al. Microbiota-Derived Hydrogen Fuels Salmonella Typhimurium Invasion of the Gut Ecosystem. Cell Host & Microbe. 2013;14(6):641-651. doi:10.1016/j.chom.2013.11.002
  • Stecher B, Maier L,Hardt WD. “Blooming” in the gut: how dysbiosis might contribute to pathogen evolution. Nat Rev Microbiol. 2013;11(4):277-284. doi:10.1038/nrmicro2989
  • Diard M, Garcia V, Maier L, et al. Stabilization of cooperative virulence by the expression of an avirulent phenotype. Nature. 2013;494(7437):353-356. doi:10.1038/nature11913