Translationale Mikrobiomforschung - Translationale Microbiome Sciences

Microbiome Sciences

Humans and other mammals have co-evolved with complex populations of microbes that constitute the microbiome. Microbes colonize mucosal surfaces, particularly of the gut, but are recently also found within organs, especially as intratumoral bacteria. The microbiome can influence many physiologic processes including metabolism and immunity, and changes in the microbiome composition can facilitate the development of disease or alter the efficacy of medical treatments. The Stein-Thoeringer laboratory studies interactions between pathogenic and beneficial bacteria within the gut microbiome and their mammalian hosts. 

Group leader

Prof. Christoph Stein-Thoeringer

Prof. Christoph Stein-Thoeringer

Oberarzt | Professor für Klinische Infektiologie und Translationale Mikrobiomforschung

Publikationen: Publikationen

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Research focus

Our laboratory’s research focuses on a wide range of commensal microbes and their metabolites to explore their effect on immune cell regulation, gut mucosal homeostasis, metabolism and tumor development. We are using in vitro culture systems and laboratory mouse models of experimental microbiome modulations, e.g., antibiotics, diet and gnotobiotics. We are sequencing and analyzing the microbiome from the gastrointestinal tract as well as low-biomass microbiomes from tumour tissue and combine various data-sets to achieve multi-omics phenotype characterizations. Our laboratory has performed several clinical microbiome studies or collaborated with clinical groups to study the role of the gut microbiome in medical conditions or in therapy outcomes.

Cancer immunotherapy with immune checkpoint inhibitors or CAR-T cells are becoming a standard-of-care for an increasing number of cancer entities, and are a viable option for a dozen of other tumor diseases. Despite promising results, these emerging new therapies necessitate precise biomarkers and predictors for treatment response and immune-related adverse events. The gut microbiome has recently emerged as a major factor determining host immunity, and previous studies have collected strong evidence that gut commensal microbes and their metabolites affect immunotherapy outcomes in mice and humans. However, the exact mechanisms and requirements remain unclear. 

Together with colleagues at the Universities of Tübingen as well as national and international collaborations, we are studying the role of the gut microbiome in the efficacy and development of toxicities of CD19-targeting CAR-T cell therapies against hematologic malignancies and of immune checkpoint inhibitors against solid tumors. We are using mouse models and conduct collaborative clinical biomarker studies. Our research focuses on the effects of diets and antibiotics on microbiome compositions, and how microbial dysbiosis can affect antitumor immunity and immune cell regulations through signaling of microbial metabolites. 

One of the most important challenges in translational microbiome research is to go beyond association and study causality. A major achievement to prove causation and study mechanisms lies within the transfer of individual microbes or whole microbiome configurations into germ-free mice. Within the new M3 – Institute at the University of Tübingen and its germ-free and gnotobiotic animal facility we are probing into mechanisms of microbe-host interactions in development of pancreatic and colon cancers and in metastasis. We have also a particular interest in the effects of the microbiome on regulation the action and toxicities of chemotherapies against these tumor entities.

Treatment with antibiotics can destroy the intestinal microbiome rendering patients vulnerable to expansion and/or colonization with Enterococcus, Klebsiella, Pseudomonas and other pathogenic gut residing bacterial species. Such a dysbiosis increases the risk for bloodstream infections in immunocompromised hosts, e.g., in patients undergoing cancer therapies. We are studying how microbiome injuries through antibiotics or diets can facilitate pathobiont expansion and colonization processes in mouse models and how these bacteria, specifically enterococci, affect mucosal homeostasis and T cell biology of the host. In clinical studies, we investigate environmental sources and transmission processes of these pathogenic bacteria within clinical settings and in vulnerable, highly immunocompromised patient cohorts. In our laboratory, we are also interested in the interaction of the microbiome with virus infections, primarily COVID-19, and microbe – immunity cross-talks that may facilitate long-term sequelae of virus infections.

Important challenges in microbiome sciences relate to targeted modulations of the gut microbiome in clinical settings. This is of particular importance for either preventing dysbiosis or restoring gut microbial homeostasis in patients receiving antibiotic treatments. In the Stein-Thoeringer laboratory we are working on identifying clinical factors, e.g., diets or chemotherapy, that are linked to antibiotic-induced microbiome dysbiosis in various patient cohorts. We are also probing into microbiome interventions through fecal microbiota transfers, dietary modifications or small molecules to change the microbiome and/or restore homeostasis as well as to modulate clinical outcomes.

IgA coating of Enterococcus faecalis in vitro by fluorescently labeled anti-IgA
IgA coating of Enterococcus faecalis in vitro by fluorescently labeled anti-IgA [green]; picture by Dr. Stein-Thoeringer
Bacteria on mucosal surfaces of the mouse gut
Bacteria on mucosal surfaces of the mouse gut: 16S rRNA FISH [green] against lectin staining of the colonic mucus [orange]; picture by Stein-Thoeringer


  • Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance.

    Suez J, Cohen Y, Valdés-Mas R, Mor U, Dori-Bachash M, Federici S, Zmora N, Leshem A, Heinemann M, Linevsky R, Zur M, Ben-Zeev Brik R, Bukimer A, Eliyahu-Miller S, Metz A, Fischbein R, Sharov O, Malitsky S, Itkin M, Stettner N, Harmelin A, Shapiro H, Stein-Thoeringer CK, Segal E, Elinav E.

    Cell. 2022 Aug 17:S0092-8674.

  • Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients.

    de Castilhos J, Zamir E, Hippchen T, Rohrbach R, Schmidt S, Hengler S, Schumacher H, Neubauer M, Kunz S, Müller-Esch T, Hiergeist A, Gessner A, Khalid D, Gaiser R, Cullin N, Papagiannarou SM, Beuthien-Baumann B, Krämer A, Bartenschlager R, Jäger D, Müller M, Herth F, Duerschmied D, Schneider J, Schmid RM, Eberhardt JF, Khodamoradi Y, Vehreschild MJGT, Teufel A, Ebert MP, Hau P, Salzberger B, Schnitzler P, Poeck H, Elinav E, Merle U, Stein-Thoeringer CK.

    Clin Infect Dis. 2022 Aug 24;75(1):e1063-e1071.

  • Alloreactive T cells deficient of the short-chain fatty acid receptor GPR109A induce less graft-versus-host disease.

    Docampo MD, da Silva MB, Lazrak A, Nichols KB, Lieberman SR, Slingerland AE, Armijo GK, Shono Y, Nguyen C, Monette S, Dwomoh E, Lee N, Geary CD, Perobelli SM, Smith M, Markey KA, Vardhana SA, Kousa AI, Zamir E, Greenfield I, Sun JC, Cross JR, Peled JU, Jenq RR, Stein-Thoeringer CK, van den Brink MRM.

    Blood. 2022 Apr 14;139(15):2392-2405.

  • Microbiome and cancer.

    Cullin N, Azevedo Antunes C, Straussman R, Stein-Thoeringer CK, Elinav E.

    Cancer Cell. 2021 Oct 11;39(10):1317-1341.

  • The Potential Role of the Intestinal Micromilieu and Individual Microbes in the Immunobiology of Chimeric Antigen Receptor T-Cell Therapy.

    Schubert ML, Rohrbach R, Schmitt M, Stein-Thoeringer CK.

    Front Immunol. 2021 May 31;12:670286.

  • Gut Microbiota-Derived Propionate Regulates the Expression of Reg3 Mucosal Lectins and Ameliorates Experimental Colitis in Mice.

    Bajic D, Niemann A, Hillmer AK, Mejias-Luque R, Bluemel S, Docampo M, Funk MC, Tonin E, Boutros M, Schnabl B, Busch DH, Miki T, Schmid RM, van den Brink MRM, Gerhard M, Stein-Thoeringer CK.

    J Crohns Colitis. 2020 Oct 5;14(10):1462-1472.

  • Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.

    Peled JU, Gomes ALC, Devlin SM, Littmann ER, Taur Y, Sung AD, Weber D, Hashimoto D, Slingerland AE, Slingerland JB, Maloy M, Clurman AG, Stein-Thoeringer CK, Markey KA, Docampo MD, Burgos da Silva M, Khan N, Gessner A, Messina JA, Romero K, Lew MV, Bush A, Bohannon L, Brereton DG, Fontana E, Amoretti LA, Wright RJ, Armijo GK, Shono Y, Sanchez-Escamilla M, Castillo Flores N, Alarcon Tomas A, Lin RJ, Yáñez San Segundo L, Shah GL, Cho C, Scordo M, Politikos I, Hayasaka K, Hasegawa Y, Gyurkocza B, Ponce DM, Barker JN, Perales MA, Giralt SA, Jenq RR, Teshima T, Chao NJ, Holler E, Xavier JB, Pamer EG, van den Brink MRM.

    N Engl J Med. 2020 Feb 27;382(9):822-834.

  • Lactose drives Enterococcus expansion to promote graft-versus-host disease.

    Stein-Thoeringer CK, Nichols KB, Lazrak A, Docampo MD, Slingerland AE, Slingerland JB, Clurman AG, Armijo G, Gomes ALC, Shono Y, Staffas A, Burgos da Silva M, Devlin SM, Markey KA, Bajic D, Pinedo R, Tsakmaklis A, Littmann ER, Pastore A, Taur Y, Monette S, Arcila ME, Pickard AJ, Maloy M, Wright RJ, Amoretti LA, Fontana E, Pham D, Jamal MA, Weber D, Sung AD, Hashimoto D, Scheid C, Xavier JB, Messina JA, Romero K, Lew M, Bush A, Bohannon L, Hayasaka K, Hasegawa Y, Vehreschild MJGT, Cross JR, Ponce DM, Perales MA, Giralt SA, Jenq RR, Teshima T, Holler E, Chao NJ, Pamer EG, Peled JU, van den Brink MRM.

    Science. 2019 Nov 29;366(6469):1143-1149.

  • An Open-Labeled Study on Fecal Microbiota Transfer in Irritable Bowel Syndrome Patients Reveals Improvement in Abdominal Pain Associated with the Relative Abundance of Akkermansia Muciniphila.

    Cruz-Aguliar RM, Wantia N, Clavel T, Vehreschild MJGT, Buch T, Bajbouj M, Haller D, Busch D, Schmid RM, Stein-Thoeringer CK.

    Digestion. 2019;100(2):127-138.

  • Nutritional Support from the Intestinal Microbiota Improves Hematopoietic Reconstitution after Bone Marrow Transplantation in Mice.

    Staffas A, Burgos da Silva M, Slingerland AE, Lazrak A, Bare CJ, Holman CD, Docampo MD, Shono Y, Durham B, Pickard AJ, Cross JR, Stein-Thoeringer C, Velardi E, Tsai JJ, Jahn L, Jay H, Lieberman S, Smith OM, Pamer EG, Peled JU, Cohen DE, Jenq RR, van den Brink MRM.

    Cell Host Microbe. 2018 Apr 11;23(4):447-457.e4.

Zertifikate und Verbände