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Chang lab

How does the intestinal microbiota influence chronic inflammation and cancer?

Introduction
Members
Cooperation Partner
Selected Publications
Third Party Funding

Schwiete Lab for Microbiota and inflammation

About 10% of the German population suffers from chronic inflammatory diseases such as rheumatism, psoriasis or intestinal inflammation. In patients, the composition of the intestinal flora (intestinal microbiota) is altered (dysbiosis) compared to healthy individuals. However, the intestinal microbiota is not only a mirror of health, but can also influence the clinical course, risk of cancer and response to therapy. Supported by the Dr. Rolf M. Schwiete Foundation, it is our aim to understand the dialogue between bacteria and the host and what role it plays in the development and chronification of inflammation.

In cooperation with the Department of Gastroenterology of the Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin and the Helmholtz Center for Environmental Research in Leipzig, our research group has developed a new method to study bacteria of the intestinal microbiota on the single cell level by flow cytometry. With this method we investigate microbiota samples from patients with chronic inflammatory bowel disease (CED), colorectal cancer and rheumatic diseases to gain a better understanding of the role of individual bacteria in chronic inflammation.

We exploit characteristics of bacteria that can be visualized by using staining reagents. Such characteristics are genome size, the coating of bacteria with endogenous antibodies, metabolic activity or sugar structures on the surface of the bacteria. By this we are investigating the composition and changes during disease and under therapy very precisely. In addition to the potential suitability of the method for monitoring the response to therapy, “microbiota cytometry” enables us to rapidly and simply compare the composition of the intestinal flora from stool samples of healthy and diseased people in order to identify bacteria associated with different diseases and to determine causal relationships. A major advantage of microbiota cytometry is the ability to sort bacteria directly from stool samples, allowing us to analyze bacteria that cannot be cultured yet.

We have already identified a bacterial genus, Anaeroplasma, that has the potential to inhibit inflammation by promoting the expression of the anti-inflammatory cytokine TGF-β, which in turn increases the production of IgA antibodies. These “mucosal” antibodies are part of the intestinal barrier that control the composition, proliferation and motility of the microbiota, contributing to the protection from uncontrolled passage of bacteria through the intestinal wall.

We have now completely sequenced the genome of Anaeroplasma and are currently deciphering the molecular mechanisms by which Anaeroplasma modulates the immune system.

Furthermore, we are developing three-dimensional small intestinal organoids to study the influence of microbial stimuli of the microflora on the intestinal barrier in cell culture. This will also allow us to reduce the number of necessarily sacrificed animals according to the 3Rs concept (Replace, Reduce, Refine).

The aim of all our research is improve our knowledge of the role of individual bacterial species in the development and maintenance of chronic inflammation and to develop new therapeutic approaches by targeted manipulation of the intestinal flora.

Keywords
Microbiota
Microbiota-Cytometry
IgA
Chronic inflammation
Cancer

Schwiete laboratory for microbiota and inflammation Dr. habil. Hyun-Dong Chang Phone +49 (0)30 28460-761 chang@drfz.de more
Group Leader
The Chang lab is supported by the Dr. Rolf M. Schwiete Foundation
Continue to Members

Group leader
Dr. rer. nat. habil. Hyun-Dong Chang

Scientists
Dr. Alexander Beller
Dr. Pawel Durek
Dr. Ute Hoffmann
Dr. René Riedel

PhD students
Lisa Budzinski, M.Sc.
Victoria von Goetze, M.Sc.
Kevin Heiking, M.Sc.
Qing Hu, Master of internal medicine
Aayushi Shah, M.Sc.

Bachelor/Diploma/Master students
Tanisha Momtaz, B. Sc.
Sabrina Freytag, B.Sc.
Mattheo Gundermann B.Sc.
Toni Sempert
Jonathan Pflüger

Technician
René Maier

Group Leader
The Chang lab is supported by the Dr. Rolf M. Schwiete Foundation
Continue to Cooperation Partner
  • Dr. Petra Bacher, IKMB – Christian-Albrechts-Universität zu Kiel, Germany
  • Dr. Charlotte Esser, Leibniz Forschungsinstitut für Umweltmedizin Düsseldorf, Germany
  • Dr. Ahmed Hegazy, Charité Universitätsmedizin Berlin, Medizinische Klinik I, Germany
  • Prof. Dr. med Kai Hildner Universitätsklinkium Erlangen
  • Dr. Kathrin Hochrath, AG Charlotte Esser, Leibniz-Institut für Umwelt-Medizinische Forschung
  • Dr. Andrey Kruglov, DRFZ, Germany
  • Dr. Anja Kühl, Charité Universitätsmedizin Berlin, Medizinische Klinik I, Germany
  • Dr. Mir-Farzin Mashreghi, DRFZ, Germany
  • Dr. Susann Müller, Helmholtz Institut für Umweltforschung, Leipzig, Germany
  • Dr. Denis Poddubnyy, Charité Universitätsmedizin Berlin, Medizinische Klinik I, Germany
  • Anne Regierer, DRFZ, Germany
  • Dr. Chiara Romagnani, Charité Universitätsmedizin Berlin, Medizinische Klinik I, Germany
  • Dr. Dagmar Scheel-Toellner, Universität Birmingham, Germany
  • Dr. Maren Schmiester, Charité Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Germany
  • Dr. Alexander Scheffold, Christian-Albrechts-Universität zu Kiel, Germany
  • Dr. Britta Siegmund, Charité Universitätsmedizin Berlin, Medizinische Klinik I, Germany
  • Dr. Rene Toes and Dr. Ulrich Scherer, Leiden University Medical Centre, The Netherlands
  • Dr. Carl Weidinger, Charité Universitätsmedizin Berlin, Medizinische Klinik I, Germany
  • Dr. Jakob Zimmermann, Universität Bern, Germany
Group Leader
The Chang lab is supported by the Dr. Rolf M. Schwiete Foundation
Continue to Selected Publications
  • Beller A, Kruglov A, Durek P, von Goetze V, Werner K, Heinz GA, Ninnemann J, Lehmann K, Maier R, Hoffmann U, Riedel R, Heiking K, Zimmermann J, Siegmund B, Mashreghi MF, Radbruch A, Chang HD. Specific microbiota enhances intestinal IgA levels by inducing TGF-β in T follicular helper cells of Peyer’s patches in mice. Eur J Immunol. 2020 Feb 17. doi: 10.1002/eji.201948474.
  • Esser C, Hochrath K, Teichweyde N, Krutmann J, Chang HD. Beyond sequencing: fast and easy microbiome profiling by flow cytometry. Arch Toxicol. 2019 Sep;93(9):2703-2704. doi: 10.1007/s00204-019-02527-1. Epub 2019 Jul 20. PubMed PMID: 31327023.
  • Chang HD, Tokoyoda K, Hoyer B, Alexander T, Khodadadi L, Mei H, Dörner T, Hiepe F, Burmester GR, Radbruch A. Pathogenic memory plasma cells in autoimmunity. Curr Opin Immunol. 2019 Oct 29;61:86-91. doi:10.1016/j.coi.2019.09.005.
  • Christian Neumann, Jonas Blume, Urmi Roy, Peggy P. Teh, Ajithkumar Vasanthakumar, Alexander Beller, Yang Liao, Frederik Heinrich, Teresita L. Arenzana, Jason A. Hackney, Celine Eidenschenk, Eric J. C. Gálvez, Christina Stehle, Gitta A. Heinz, Patrick Maschmeyer, Tom Sidwell, Yifang Hu, Derk Amsen, Chiara Romagnani, Hyun-Dong Chang, Andrey Kruglov, Mir-Farzin Mashreghi, Wei Shi, Till Strowig, Sascha Rutz, Axel Kallies and Alexander Scheffold; c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host–microbiota homeostasis; Nature Immunology 2019
  • H, Dela Cruz GV, Eck S, Elliott J, Errington R, Filby A, Gagnon D, Gardner R, Green C, Gregory M, Groves CJ, Hall C, Hammes F, Hedrick M, Hoffman R, Icha J, Ivaska J, Jenner DC, Jones D, Kerckhof FM, Kukat C, Lanham D, Leavesley S, Lee M, Lin-Gibson S, Litwin V, Liu Y, Molloy J, Moore JS, Müller S, Nedbal J, Niesner R, Nitta N, Ohlsson-Wilhelm B, Paul NE, Perfetto S, Portat Z, Props R, Radtke S, Rayanki R, Rieger A, Rogers S, Rubbens P, Salomon R, Schiemann M, Sharpe J, Sonder SU, Stewart JJ, Sun Y, Ulrich H, Van Isterdael G, Vitaliti A, van Vreden C, Weber M, Zimmermann J, Vacca G, Wallace P, Tárnok A. Cyt-Geist: Current and Future Challenges in Cytometry: Reports of the CYTO 2018 Conference Workshops. Cytometry A. 2019 Jun;95(6):598-644. doi: 10.1002/cyto.a.23777. PubMed PMID: 31207046.
  • Cossarizza A, Chang HD, Radbruch A et al Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur J Immunol. 2019 Oct;49(10):1457-1973. doi: 10.1002/eji.201970107.
  • Zimmermann J, Durek P, Kühl AA, Schattenberg F, Maschmeyer P, Siracusa F, Lehmann K, Westendorf K, Weber M, Riedel R, Müller S, Radbruch A, Chang HD. The intestinal microbiota determines the colitis-inducing potential of T-bet-deficient Th cells in mice. Eur J Immunol. 2018 Jan;48(1):161-167. doi: 10.1002/eji.201747100.
Group Leader
The Chang lab is supported by the Dr. Rolf M. Schwiete Foundation
Continue to Third Party Funding
  • Rolf M. Schwiete Stiftung
  • TRR130 Teilprojekt 16 (Radbruch/Chang): Deciphering the Survival Code of Memory Plasma Cells and Memory B Cells
  • TRR241 Teilprojekt B03 (Chang/Radbruch): The intestinal epithelial cells in the dialogue between microbiota and the immune system
  • EU H2020 IMI2 RTCure: WP3 (Project leader Chang/Radbruch)
  • EU H2020 IMI2 3TR
Group Leader
The Chang lab is supported by the Dr. Rolf M. Schwiete Foundation
Continue to Introduction