Microbial modulation of glycolysis and its impact on inflammation and cancer

Research group P5

Introduction

Glycolysis regulation by hexokinase is emerging as a key feature of all cells with a high energetic demand, cells performing an immune response and rapidly proliferating cancer cells. Several lines of evidence link hexokinase and glycolysis regulation to controlling immune responses. The molecular details of the regulatory mechanisms of the metabolic reprogramming during an inflammatory response have only begun to be unraveled.

Aims

The overall aim of this project is to investigate how the microbiota regulate hexokinase activity and glycolysis in the intestinal epithelium and how this regulation influences host physiology in health and disease. More specifically, we will examine the molecular network controlling the expression and function of the microbiota-responsive hexokinase and determine its involvement in intestinal mucosal immune responses and carcinogenesis.

Fig. 1: Main objectives and aims of the study

Outlook

This project promises to identify hexokinase and glycolysis regulation by the microbiota as key determinant in the control of inflammation or carcinogenesis. Further studies targeting specific functions of the microbiota through dietary, probiotic or pharmacological approaches may unravel new therapeutic options for intestinal chronic inflammation and cancer.


Project-related publications

P5

DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon.

Antonella Fazio, Dora Bordoni, Jan W P Kuiper, Saskia Weber-Stiehl, Stephanie T Stengel, Philipp Arnold, David Ellinghaus, Go Ito, Florian Tran, Berith Messner, Anna Henning, Joana P Bernardes, Robert Häsler, Anne Luzius, Simon Imm, Finn Hinrichsen, Andre Franke, Samuel Huber, Susanna Nikolaus, Konrad Aden, Stefan Schreiber, Felix Sommer, Gioacchino Natoli, Neha Mishra, Philip Rosenstiel

Nature communications
2022
P5

Endoplasmic reticulum stress in the intestinal epithelium initiates purine metabolite synthesis and promotes Th17 cell differentiation in the gut.

Jinzhi Duan, Juan D Matute, Lukas W Unger, Thomas Hanley, Alexandra Schnell, Xi Lin, Niklas Krupka, Paul Griebel, Conner Lambden, Brandon Sit, Joep Grootjans, Michal Pyzik, Felix Sommer, Sina Kaiser, Maren Falk-Paulsen, Helmut Grasberger, John Y Kao, Tobias Fuhrer, Hai Li, Donggi Paik, Yunjin Lee, Samuel Refetoff, Jonathan N Glickman, Adrienne W Paton, Lynn Bry, James C Paton, Uwe Sauer, Andrew J Macpherson, Philip Rosenstiel, Vijay K Kuchroo, Matthew K Waldor, Jun R Huh, Arthur Kaser, Richard S Blumberg

Immunity (Cambridge, Mass.)
2023
P5

A gut bacterial signature in blood and liver tissue characterizes cirrhosis and hepatocellular carcinoma.

Maria Effenberger, Silvio Waschina, Christina Bronowski, Gregor Sturm, Oronzo Tassiello, Felix Sommer, Andreas Zollner, Christina Watschinger, Felix Grabherr, Ronald Gstir, Christoph Grander, Barbara Enrich, Reto Bale, Daniel Putzer, Angela Djanani, Alexander R Moschen, Heinz Zoller, Jan Rupp, Stefan Schreiber, Remy Burcelin, Cornelia Lass-Flörl, Zlatko Trajanoski, Georg Oberhuber, Philip Rosenstiel, Timon E Adolph, Konrad Aden, Herbert Tilg

Hepatology communications
2023
P5

Commensal bacteria weaken the intestinal barrier by suppressing epithelial neuropilin-1 and Hedgehog signaling.

Giulia Pontarollo, Bettina Kollar, Amrit Mann, My Phung Khuu, Klytaimnistra Kiouptsi, Franziska Bayer, Inês Brandão, Valeriya V Zinina, Jennifer Hahlbrock, Frano Malinarich, Maximilian Mimmler, Sudhanshu Bhushan, Federico Marini, Wolfram Ruf, Meriem Belheouane, John F Baines, Kristina Endres, Scott M Reba, Verena K Raker, Carsten Deppermann, Christoph Welsch, Markus Bosmann, Natalia Soshnikova, Benoit Chassaing, Mattias Bergentall, Felix Sommer, Fredrik Bäckhed, Christoph Reinhardt

Nature metabolism
2023
P5

Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis.

Finn Hinrichsen, Jacob Hamm, Magdalena Westermann, Lena Schröder, Kensuke Shima, Neha Mishra, Alesia Walker, Nina Sommer, Kenneth Klischies, Daniela Prasse, Johannes Zimmermann, Sina Kaiser, Dora Bordoni, Antonella Fazio, Georgios Marinos, Georg Laue, Simon Imm, Valentina Tremaroli, Marijana Basic, Robert Häsler, Ruth A Schmitz, Stefan Krautwald, Andrea Wolf, Bärbel Stecher, Philippe Schmitt-Kopplin, Christoph Kaleta, Jan Rupp, Fredrik Bäckhed, Philip Rosenstiel, Felix Sommer

Cell metabolism
2021
P5

PUFA-induced metabolic enteritis as a fuel for Crohn’s disease.

Julian Schwärzler, Lisa Mayr, Arnau Vich Vila, Felix Grabherr, Lukas Niederreiter, Maureen Philipp, Christoph Grander, Moritz Meyer, Almina Jukic, Simone Tröger, Barbara Enrich, Nicole Przysiecki, Markus Tschurtschenthaler, Felix Sommer, Irmgard Kronberger, Jakob Koch, Richard Hilbe, Michael W Hess, Georg Oberhuber, Susanne Sprung, Qitao Ran, Robert Koch, Maria Effenberger, Nicole C Kaneider, Verena Wieser, Markus A Keller, Rinse K Weersma, Konrad Aden, Philip Rosenstiel, Richard S Blumberg, Arthur Kaser, Herbert Tilg, Timon E Adolph

Gastroenterology (New York, N.Y. 1943)
2022
P5

Precision Nutrition in Chronic Inflammation.

Tobias J Demetrowitsch, Kristina Schlicht, Carina Knappe, Johannes Zimmermann, Julia Jensen-Kroll, Alina Pisarevskaja, Fynn Brix, Juliane Brandes, Corinna Geisler, Georgios Marinos, Felix Sommer, Dominik M Schulte, Christoph Kaleta, Vibeke Andersen, Matthias Laudes, Karin Schwarz, Silvio Waschina

Frontiers in immunology
2020
P5

Short-term physical exercise impacts on the human holobiont obtained by a randomised intervention study.

Lucas Moitinho-Silva, Michelle Wegener, Sandra May, Florian Schrinner, Awais Akhtar, Teide J Boysen, Eva Schaeffer, Clint Hansen, Timo Schmidt, Malte C Rühlemann, Matthias Hübenthal, Philipp Rausch, Mustafa T Kondakci, Walter Maetzler, Stephan Weidinger, Matthias Laudes, Philip Süß, Dominik Schulte, Ralf Junker, Felix Sommer, Burkhard Weisser, Corinna Bang, Andre Franke

BMC microbiology
2021

Researchers

Lea Järke

Doctoral Researcher, Associated Scientist
Institute of Clinical Molecular Biology (IKMB) / Kiel University (CAU), University Medical Center Schleswig-Holstein (UKSH)
P5 (Phase 1),
P4 (Phase 2)

Other important members of P5

  • Dr. Neha Mishra, bioinformatician
  • Dr. Joana Pimenta Bernardes, bioinformatician
  • Dr. Sören Franzenburg, head of the NGS laboratory
  • Jacob Hamm, medical PhD student
  • Finn Hinrichsen, medical PhD student
  • Kenneth Klischies, medical PhD student

Participating Institutes