TI-1: The Microbiome as a Modifier of Immune-modulatory Therapies

Coordinators: J. Baines (CAU, MPI), P. Rosenstiel (CAU), C. Sadik (UzL)

In TI-1, the members systematically investigate whether and how the microbiome, i.e. the totality of microorganisms colonizing the skin or intestine, for example, influences the individual respond to therapy in chronic inflammatory diseases. This is being investigated using the example of inflammatory bowel disease (IBD) and bullous pemphigoid (BP). The results could help provide personalized treatment recommendations and develop microbiome-based therapies to optimize the treatment of chronic inflammatory diseases.

What does this research area's work build on?

In recent years, more and more research has provided evidence that at the site of inflammation in all chronic inflammatory barrier diseases (CIBD), the microbiome is out of balance. In inflammatory bowel disease (IBD), the phenomenon was initially attributed to the direct effect of local inflammation leading to gross alterations in the properties of the intestinal mucosa. However, recent evidence has shown that the gut microbiome is actually disrupted in many CIBDs, including rheumatoid arthritis and even skin diseases. It remains unclear whether this dysbiosis arises from the over-activated host cytokine network that actively shapes the gut microbiome, or was present prior to the primary disease, making patients more susceptible to it. Nonetheless, recent cancer therapy studies have shown that in these cases the microbiome can help predict or account for individual therapy response. The efficacy of the immunomodulatory anticancer drug cyclophosphamide depends on the composition of the gut microbiota and its recognition by the innate immune receptor NOD2.  Other studies have shown that patients undergoing anti-PD-1 immunotherapy for the treatment of melanoma can be easily classified into responders and non-responders based on their gut microbiome, and have demonstrated the causal contribution to treatment response by fecal microbiota transplantation (FMT) into germ-free mice. Participants in TI-1 suggest that the gut (and skin) microbiome influences individual response to targeted therapies in CIBD as well.

 

What are the main research objectives?

TI-1 has the following main objectives:

  • Perform multi-omics profiling of the microbiome during the course of treatment for IBD and BP diseases.
  • Identify taxonomic and functional metagenomic indicators of responders vs. non-responders for individual treatments.
  • Validate the impact of indicators of responders vs. non-responders in preclinical studies using humanized gnotobiotic mouse models.
  • Develop algorithms for individualized microbiome-based treatment recommendations.
  • Investigate microbiome-based interventional approaches (e.g., postbiotics) to optimize treatment.

What makes this research area special?

The project has the potential to demonstrate that the microbiome influences the response to CIBD therapy. To date, this relationship has only been demonstrated in a few exemplary diseases. This will significantly advance knowledge of these diseases and provide the basis for translation into the clinic.

What does the research area contribute to precision medicine in chronic inflammation?

The results of TI-1 will allow to determine individual therapeutic decisions based on the microbiome of individual patients.

Cooperation with other research areas in the cluster

TI-1 will work closely with RTF X and CD-1 to access material from patients and prospective cohorts. The preclinical animal models will be performed in collaboration with RTF IV.

Members

Dr. Nadia Andreani

Associated member

Max Planck Institute for Evolutionary Biology
Institute of Experimental Medicine
AG Prof. Baines

Prof. Dr. John Baines

Full member

Max Planck Institute for Evolutionary Biology
Institute of Experimental Medicine
Evolutionary Genomics

Dr. rer. nat. Corinna Bang

Assocciated member

Kiel University
Institute of Clinical Molecular Biology
AG Prof. Franke

Prof. Dr. med. Thorsten Bartsch

Full member

UKSH Campus Kiel
Department of Neurology

Prof. Dr. Christoph Becker-Pauly

Full member

Kiel University
Institute of Biochemistry
Degradomics of the Protease Web

Dr. Meriem Belheouane

Associated member

Research Center Borstel - Leibniz Lung Center
Evolution of the Resistome
Priority Research Area Infections
AG Prof. Merker

PD Dr. Katja Bieber

Associated member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology

Prof. Dr. Hauke Busch

Full member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
System Biology of Inflammatory Diseases

Prof. Dr. Christof Dörfer

Full member

UKSH Campus Kiel
Department of Dental Conservation Customer and Periodontology

Prof. Dr. Marc Ehlers

Full member

UKSH Campus Lübeck
Institute of Medical Nutrition Science
Immunology and Glycoanalytics

Dr. rer. nat. Maren Falk-Paulsen

Associated member

Kiel University
Institute of Clinical Molecular Biology
RG Prof. Rosenstiel

Prof. Dr. rer. nat. Andre Franke

Full member

Kiel University
Institute of Clinical Molecular Biology
Genetics & Bioinformatics

Prof. Dr. Timo Gemoll

Associated member

UKSH Campus Lübeck
Department of General Surgery

Prof. Dr. med. Regine Gläser

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Dr. rer. nat. Simon Graspeuntner

Associated member

UKSH Campus Lübeck
Department of Infectious Diseases and Microbiology
AG Prof. Rupp

Martina Guggeis

Associated member

Kiel University
Institute of Clinical Molecular Biology
AG Prof. Rosenstiel

Dr. rer. hum. biol. Yask Gupta

Associated member

UKSH Campus Lübeck
Institute for Inflammation Medicine
AG Prof. Thaçi

Prof. Dr. rer. nat. Jürgen Harder

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology

Prof. Dr. rer. nat. Markus Hoffmann

Full member

UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology

Prof. Dr. Saleh Ibrahim

Full member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Genetics of Inflammatory Diseases

Lea Järke

Associated member

Kiel University
Institute of Clinical Molecular Biology
AG PD Sommer

Prof. Dr. Christoph Kaleta

Full member

UKSH Campus Kiel
Institute of Experimental Medicine
c/o Transfusion Medicine

Dr. rer. nat. Anika Kasprick

Associated member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
AG Prof. Ludwig

Prof. Dr. rer. nat. Ben Krause-Kyora

Full member

Kiel University
Institute of Clinical Molecular Biology
Ancient DNA Research

Prof. Dr. med. Matthias Laudes

Full member

UKSH Campus Kiel
Institute of Diabetes and Clinical Metabolic Research

PD Dr. Yves Laumonnier

Associated member

University of Lübeck
Institute for Systemic Inflammation Research

Prof. Dr. Ralf Ludwig

Full member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Model Systems of Inflammatory Skin Diseases

Prof. Dr. rer. nat. Silke Meiners

Full member

Kiel University
Institute of Experimental Medicine

c/o Research Center Borstel - Leibniz Lung Center
Immunology and Cell Biology
Priority Research Area Chronic Lung Diseases

Prof. Dr. Matthias Merker

Full member

Research Center Borstel - Leibniz Lung Center
Evolution of the Resistome
Priority Research Area Infections

Prof. Dr. Ulrich Mrowietz

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology
Psoriasis-Center

Dr. Wiebke Prüßmann

Associated member

UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology

Prof. Dr. Gabriela Riemekasten

Full member

UKSH Campus Lübeck
Department of Rheumatology and Clinical Immunology

Prof. Dr. med. Christoph Röcken

Full member

UKSH Campus Kiel
Institute of Pathology

Prof. Dr. Stefan Rose-John

Full member

Kiel University
Institute of Biochemistry
Cytokine and Metalloproteinase Research

Prof. Dr. med. Philip Rosenstiel

Full member

Kiel University
Institute of Clinical Molecular Biology
Systems Immunology

Prof. Dr. Jan Rupp

Full member

UKSH Campus Lübeck
Department of Infectious Diseases and Microbiology

Prof. Dr. Christian Sadik

Full member

UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology
Innate immunity

Prof. Dr. rer. nat. Alexander Scheffold

Full member

UKSH Campus Kiel
Department of Immunology

Prof. Dr. Dr. Enno Schmidt

Full member

UKSH Campus Lübeck
Lübeck Institute for Experimental Dermatology
Translational Research

Prof. Dr. rer. nat. Ruth Schmitz-Streit

Full member

Kiel University
Institute of General Microbiology
Molecular Biology of Microorganisms

Prof. Dr. med. Stefan Schreiber

Spokesperson

Kiel University
Institute of Clinical Molecular Biology

Prof. Dr. Hinrich Schulenburg

Full member

Kiel University
Institute of Zoology
Evolutionary Ecology and Genetics

Prof. Dr. Christian Sina

Full member

UKSH Campus Lübeck
Institute of Medical Nutrition Science

Dr. rer. nat. Felix Sommer

Full member

UKSH Campus Kiel
Institute of Clinical Molecular Biology
Functional Host-Microbiome Research

Prof. Dr. Diethard Tautz

Full member

Max Planck Institute for Evolutionary Biology
Evolutionary Genetics

Dr. Daniel Unterweger

Full member

Max Planck Institute for Evolutionary Biology
Institute of Experimental Medicine

Prof. Dr. med. Thomas Valerius

Full member

UKSH Campus Kiel
Department of Internal Medicine II
Stem Cells and Immunotherapy

Dr. Artem Vorobyev

Associated member

UKSH Campus Lübeck
Department of Dermatology, Allergology and Venerology

Dr. Georg Wätzig

Associated member

UKSH Campus Kiel
Institute of Clinical Molecular Biology

Prof. Dr. Stephan Weidinger

Full member

UKSH Campus Kiel
Department of Dermatology, Venereology and Allergology