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.

Interview

Drug-Microbiome-Host-Interactions – Interview with Prof. Dr. rer. nat. Lisa Maier

In this interview, we explore groundbreaking research into the direct impact of medicinal drugs, especially cancer and psychotropic treatments, on the human gut microbiome. Find out how the team uses microbiology-driven methods to map the effects of drugs on gut bacteria, reveal the underlying molecular mechanisms and examine the consequences for health and disease. Find out about the innovative strategies being employed to combat the harmful effects of gut colonisation associated with malnutrition and colorectal cancer, and how scientists are unravelling the secrets of lesser-known gut microbes to improve our understanding of the intricate microbial ecosystem within us.

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  • 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

  • 2025

    Antagonistic drug interactions protect commensal Bacteroidaceae from macrolides via an RND-type efflux pump

    Müller P, Schmidtchen V, de la Cuesta-Zuluaga J, Pérez Jiménez L, Gekeler C, Mateus A, Maier L. Antagonistic drug interactions protect commensal Bacteroidaceae from macrolides via an RND-type efflux pump.
    Gut Microbes. 2025 Dec 31;17(1):2596806. doi: 10.1080/19490976.2025.2596806. Epub 2025 Dec 9. PMID: 41362921; PMCID: PMC12694919. https://doi.org/10.1080/19490976.2025.2596806
  • 2025

    ). CFTR modulator therapy drives microbiome restructuring through improved host physiology in cystic fibrosis: The IMMProveCF phase IV trial

    Knoll RL, Brauny MM, Robert E, Cloos L, Waser L, Hilbert K, Ulmer N, Hillen B, Birkner T, Bartolomaeus TUP, Nitsche O, Jarquín-Díaz VH, Lynch S, Gehring S, Maier L, Poplawska K, Forslund-Startceva SK. CFTR modulator therapy drives microbiome restructuring through improved host physiology in cystic fibrosis: the IMMProveCF phase IV trial.
    Nat Commun. 2025 Nov 18;16(1):10111. https://doi.org/10.1038/s41467-025-64218-z
  • 2025

    Industrial and agricultural chemicals exhibit antimicrobial activity against human gut bacteria in vitro

    Roux I, Lindell AE, Grießhammer A, Smith T, Krishna S, Guan R, Rad D, Faria L, Blasche S, Patil KR, Kleinstreuer NC, Maier L, Kamrad S, Patil KR. Industrial and agricultural chemicals exhibit antimicrobial activity against human gut bacteria in vitro.
    Nat Microbiol. 2025 Dec;10(12):3107-3121. doi: 10.1038/s41564-025-02182-6. Epub 2025 Nov 26. PMID: 41299073; PMCID: PMC12669032. https://doi.org/10.1038/s41564-025-02182-6
  • 2025

    Modulation of bacterial cell size and growth rate via activation of a cell envelope stress response

    Miguel A, Zietek M, Shi H, Sueki A, Corona F, Maier L, Verheul J, den Blaauwen T, Van Valen D, Typas A, Huang KC. Modulation of bacterial cell size and growth rate via activation of a cell envelope stress response.
    mBio. 2025 Nov 12;16(11):e0228125. doi: 10.1128/mbio.02281-25. Epub 2025 Sep 22. PMID: 40980883; PMCID: PMC12607864.

    https://doi.org/10.1128/mbio.02281-25
  • 2025

    Non-antibiotics disrupt colonization resistance against enteropathogens

    Grießhammer A, de la Cuesta-Zuluaga J, Müller P, Gekeler C, Homolak J, Chang H, Schmitt K, Planker C, Schmidtchen V, Gallage S, Bohn E, Nguyen TH, Hetzer J, Heikenwälder M, Huang KC, Zahir T, Maier L. Non-antibiotics disrupt colonization resistance against enteropathogens.
    Nature. 2025 Aug;644(8076):497-505. doi: 10.1038/s41586-025-09217-2. Epub 2025 Jul 16. PMID: 40670795; PMCID: PMC12350171.

    https://doi.org/10.1038/s41586-025-09217-2
  • 2025

    Human gut bacteria bioaccumulate per- and polyfluoroalkyl substances

    Lindell AE, Grießhammer A, Michaelis L, Papagiannidis D, Ochner H, Kamrad S, Guan R, Blasche S, Ventimiglia LN, Ramachandran B, Ozgur H, Zelezniak A, Beristain-Covarrubias N, Yam-Puc JC, Roux I, Barron LP, Richardson AK, Martin MG, Benes V, Morone N, Thaventhiran JED, Bharat TAM, Savitski MM, Maier L, Patil KR. Human gut bacteria bioaccumulate per- and polyfluoroalkyl substances.
    Nat Microbiol. 2025 Jul;10(7):1630-1647. doi: 10.1038/s41564-025-02032-5. Epub 2025 Jul 1. PMID: 40595288; PMCID: PMC12222025. https://doi.org/10.1038/s41564-025-02032-5
  • 2025

    Proton-pump inhibitors increase C. difficile infection risk by altering pH rather than by affecting the gut microbiome based on a bioreactor model

    Schumacher J, Müller P, Sulzer J, Faber F, Molitor B, Maier L. Proton-pump inhibitors increase C. difficile infection risk by altering pH rather than by affecting the gut microbiome based on a bioreactor model.
    Gut Microbes. 2025 Dec;17(1):2519697. doi: 10.1080/19490976.2025.2519697. Epub 2025 Jun 16. PMID: 40524314; PMCID: PMC12184164. https://doi.org/10.1080/19490976.2025.2519697
  • 2025

    Enabling next-generation anaerobic cultivation through biotechnology to advance functional microbiome research

    Clavel T, Faber F, Groussin M, Haller D, Overmann J, Pauvert C, Poyet M, Selkrig J, Stecher B, Typas A, Vehreschild MJGT, Westermann AJ, Wylensek D, Maier L. Enabling next-generation anaerobic cultivation through biotechnology to advance functional microbiome research.
    Nat Biotechnol. 2025 Jun;43(6):878-888. doi: 10.1038/s41587-025-02660-6. Epub 2025 Apr 29. PMID: 40301656. https://doi.org/10.1038/s41587-025-02660-6
  • 2025

    An anti-virulence drug targeting the evolvability protein Mfd protects against infections with antimicrobial resistant ESKAPE pathogens

    Tran SL, Lebreuilly L, Cormontagne D, Samson S, Tô TB, Stosskopf M, Dervyn R, Grießhammer A, de la Cuesta-Zuluaga J, Maier L, Naas T, Mura S, Rognan D, Nicolas J, André G, Ramarao N. An anti-virulence drug targeting the evolvability protein Mfd protects against infections with antimicrobial resistant ESKAPE pathogens.
    Nat Commun. 2025 Apr 28;16(1):3324. https://doi.org/10.1038/s41467-025-58282-8
  • 2025

    Sublethal systemic LPS in mice enables gut-luminal pathogens to bloom through oxygen species-mediated microbiota inhibition

    Kroon S, Malcic D, Weidert L, Bircher L, Boldt L, Christen P, Kiefer P, Sintsova A, Nguyen BD, Barthel M, Steiger Y, Clerc M, Herzog MK, Chen C, Gül E, Guery B, Slack E, Sunagawa S, Vorholt JA, Maier L, Lacroix C, Hausmann A, Hardt WD. Sublethal systemic LPS in mice enables gut-luminal pathogens to bloom through oxygen species-mediated microbiota inhibition.
    Nat Commun. 2025 Mar 20;16(1):2760. https://doi.org/10.1038/s41467-025-57979-0
  • 2024

    Balancing Act: Counteracting Adverse Drug Effects on the Microbiome

    de la Cuesta-Zuluaga J, Müller P, Maier L. Balancing act: counteracting adverse drug effects on the microbiome.
    Trends Microbiol. 2025 Mar;33(3):268-276. doi: 10.1016/j.tim.2024.09.011. Epub 2024 Oct 11. PMID: 39395850. https://doi.org/10.1016/j.tim.2024.09.011
  • 2024

    ) Emergence of community behaviors in the gut microbiota upon drug treatment

    Garcia-Santamarina S, Kuhn M, Devendran S, Maier L, Driessen M, Mateus A, Mastrorilli E, Brochado AR, Savitski MM, Patil KR, Zimmermann M, Bork P, Typas A. Emergence of community behaviors in the gut microbiota upon drug treatment.
    Cell. 2024 Oct 31;187(22):6346-6357.e20. doi: 10.1016/j.cell.2024.08.037. Epub 2024 Sep 24. PMID: 39321801. https://doi.org/10.1016/j.cell.2024.08.037
  • 2024

    Response, resistance, and recovery of gut bacteria to human-targeted drug exposure

    de la Cuesta-Zuluaga J, Boldt L, Maier L. Response, resistance, and recovery of gut bacteria to human-targeted drug exposure.
    Cell Host Microbe. 2024 Jun 12;32(6):786-793. https://doi.org/10.1016/j.chom.2024.05.009
  • 2024

    Integrating research on bacterial pathogens and commensals to fight infections—an ecological perspective

    Maier L, Stein-Thoeringer C, Ley RE, Brötz-Oesterhelt H, Link H, Ziemert N, Wagner S, Peschel A. Integrating research on bacterial pathogens and commensals to fight infections-an ecological perspective.
    Lancet Microbe. 2024 Aug;5(8):100843. doi: 10.1016/S2666-5247(24)00049-1. Epub 2024 Apr 9. PMID: 38608681.

    https://doi.org/10.1016/s2666-5247(24)00049-1
  • 2024

    Antimicrobial Evaluation of Two Polycyclic Polyprenylated Acylphloroglucinol Compounds: PPAP23 and PPAP53

    Ammanath AV, Matsuo M, Wang H, Kraus F, Bleisch A, Peslalz P, Mohammad M, Deshmukh M, Grießhammer A, Purkayastha M, Vorbach A, Macek B, Brötz-Oesterhelt H, Maier L, Kretschmer D, Peschel A, Jin T, Plietker B, Götz F. Antimicrobial Evaluation of Two Polycyclic Polyprenylated Acylphloroglucinol Compounds: PPAP23 and PPAP53.
    Int J Mol Sci. 2024 Jul 23;25(15):8023. https://doi.org/10.3390/ijms25158023
  • 2024

    High-Throughput Screening Strategies for Identifying Compounds Acting against Gut Bacteria

    Müller P, de la Cuesta-Zuluaga J, Kuhn M, Baghai Arassi M, Treis T, Blasche S, Zimmermann M, Bork P, Patil KR, Typas A, Garcia-Santamarina S, Maier L. High-throughput anaerobic screening for identifying compounds acting against gut bacteria in monocultures or communities.
    Nat Protoc. 2024 Mar;19(3):668-699. doi: 10.1038/s41596-023-00926-4. Epub 2023 Dec 13. PMID: 38092943.

    https://doi.org/10.1038/s41596-023-00926-4
  • 2021

    Unravelling the collateral damage of antibiotics on gut bacteria

    Maier L, Goemans CV, Wirbel J, Kuhn M, Eberl C, Pruteanu M, Müller P, Garcia-Santamarina S, Cacace E, Zhang B, Gekeler C, Banerjee T, Anderson EE, Milanese A, Löber U, Forslund SK, Patil KR, Zimmermann M, Stecher B, Zeller G, Bork P, Typas A. Unravelling the collateral damage of antibiotics on gut bacteriaNature. 2021 Nov;599(7883):120-124. doi: 10.1038/s41586-021-03986-2. Epub 2021 Oct 13. PMID: 34646011; PMCID: PMC7612847. https://doi.org/10.1038/s41586-021-03986-2
  • 2021

    Bioaccumulation of therapeutic drugs by human gut bacteria

    Klünemann M, Andrejev S, Blasche S, Mateus A, Phapale P, Devendran S, Vappiani J, Simon B, Scott TA, Kafkia E, Konstantinidis D, Zirngibl K, Mastrorilli E, Banzhaf M, Mackmull MT, Hövelmann F, Nesme L, Brochado AR, Maier L, Bock T, Periwal V, Kumar M, Kim Y, Tramontano M, Schultz C, Beck M, Hennig J, Zimmermann M, Sévin DC, Cabreiro F, Savitski MM, Bork P, Typas A, Patil KR. Bioaccumulation of therapeutic drugs by human gut bacteriaNature. 2021 Sep;597(7877):533-538. doi: 10.1038/s41586-021-03891-8. Epub 2021 Sep 8. PMID: 34497420; PMCID: PMC7614428. https://doi.org/10.1038/s41586-021-03891-8
  • 2021

    Towards a mechanistic understanding of reciprocal drug-microbiome interactions

    Zimmermann M, Patil KR, Typas A, Maier L. Towards a mechanistic understanding of reciprocal drug-microbiome interactions.
    Mol Syst Biol. 2021 Mar;17(3):e10116. https://doi.org/10.15252/msb.202010116
  • 2019

    Escherichia coli limits Salmonella Typhimurium infections after diet shifts and fat-mediated microbiota perturbation in mice

    Wotzka SY, Kreuzer M, Maier L, Arnoldini M, Nguyen BD, Brachmann AO, Berthold DL, Zünd M, Hausmann A, Bakkeren E, Hoces D, Gül E, Beutler M, Dolowschiak T, Zimmermann M, Fuhrer T, Moor K, Sauer U, Typas A, Piel J, Diard M, Macpherson AJ, Stecher B, Sunagawa S, Slack E, Hardt WD. Escherichia coli limits Salmonella Typhimurium infections after diet shifts and fat-mediated microbiota perturbation in miceNat Microbiol. 2019 Dec;4(12):2164-2174. doi: 10.1038/s41564-019-0568-5. Epub 2019 Oct 7. PMID: 31591555; PMCID: PMC6881180. https://doi.org/10.1038/s41564-019-0568-5
  • 2018

    Extensive impact of non-antibiotic drugs on human gut bacteria

    Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, Brochado AR, Fernandez KC, Dose H, Mori H, Patil KR, Bork P, Typas A. Extensive impact of non-antibiotic drugs on human gut bacteria.
    Nature. 2018 Mar 29;555(7698):623-628. doi: 10.1038/nature25979. Epub 2018 Mar 19. PMID: 29555994; PMCID: PMC6108420. https://doi.org/10.1038/nature25979
  • 2017

    Salt-responsive gut commensal modulates TH17 axis and disease

    Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, Haase S, Mähler A, Balogh A, Markó L, Vvedenskaya O, Kleiner FH, Tsvetkov D, Klug L, Costea PI, Sunagawa S, Maier L, Rakova N, Schatz V, Neubert P, Frätzer C, Krannich A, Gollasch M, Grohme DA, Côrte-Real BF, Gerlach RG, Basic M, Typas A, Wu C, Titze JM, Jantsch J, Boschmann M, Dechend R, Kleinewietfeld M, Kempa S, Bork P, Linker RA, Alm EJ, Müller DN. Salt-responsive gut commensal modulates TH17 axis and diseaseNature. 2017 Nov 30;551(7682):585-589. https://doi.org/10.1038/nature24628
  • 2014

    Granulocytes impose a tight bottleneck upon the gut luminal pathogen population during Salmonella typhimurium colitis

    Maier L, Diard M, Sellin ME, Chouffane ES, Trautwein-Weidner K, Periaswamy B, Slack E, Dolowschiak T, Stecher B, Loverdo C, Regoes RR, Hardt WD. Granulocytes impose a tight bottleneck upon the gut luminal pathogen population during Salmonella typhimurium colitisPLoS Pathog. 2014 Dec 18;10(12):e1004557. doi: 10.1371/journal.ppat.1004557. Erratum in: PLoS Pathog. 2015 Jul 17;11(7):e1005047. doi: 10.1371/journal.ppat.1005047. PMID: 25522364; PMCID: PMC4270771. https://doi.org/10.1371/journal.ppat.1004557
  • 2013

    Stabilization of cooperative virulence by the expression of an avirulent phenotype

    Diard M, Garcia V, Maier L, Remus-Emsermann MN, Regoes RR, Ackermann M, Hardt WD. Stabilization of cooperative virulence by the expression of an avirulent phenotype.
    Nature. 2013 Feb 21;494(7437):353-6. https://doi.org/10.1038/nature11913
  • 2013

    Microbiota-derived hydrogen fuels Salmonella typhimurium invasion of the gut ecosystem

    Maier L, Vyas R, Cordova CD, Lindsay H, Schmidt TS, Brugiroux S, Periaswamy B, Bauer R, Sturm A, Schreiber F, von Mering C, Robinson MD, Stecher B, Hardt WD. Microbiota-derived hydrogen fuels Salmonella typhimurium invasion of the gut ecosystemCell Host Microbe. 2013 Dec 11;14(6):641-51. https://doi.org/10.1016/j.chom.2013.11.002
  • 2013

    'Blooming' in the gut: how dysbiosis might contribute to pathogen evolution

    Stecher B, Maier L, Hardt WD. 'Blooming' in the gut: how dysbiosis might contribute to pathogen evolution. Nat Rev Microbiol. 2013 Apr;11(4):277-84. doi: 10.1038/nrmicro2989. Epub 2013 Mar 11. PMID: 23474681. https://doi.org/10.1038/nrmicro2989