mTORUS – Microbiome-based Therapeutic Options for Recurrent Urinary Symptoms

Problem Recurring urinary tract infections and antibiotic resistance

Goal Restoration of a healthy urinary microbiome through elimination of bacteria and microbiome transplantation

Recurrent urinary tract infections are widespread and represent a significant burden for those affected. The goal of the mTORUS project is to restore a healthy microbiome of the urinary tract. This is to be achieved through a two-step treatment: first, the pathogenic bacteria are eliminated using genetically modified bacteriophages (PUSH). Subsequently, a “healthy” bacterial population is established in the bladder through a microbiome transplantation (PULL). This approach, combined with strengthening of the immune system, will help preventing recurring infections. To this end, the team led by Thomas M. Kessler is researching the composition of a healthy urinary tract microbiome and analyzing how infections alter the microbiome and immune system.

In the first phase of the project, the researchers have already made the following progress: they optimized methods for sample collection, processing, and analysis involving several laboratories; conducted a successful microbiome validation study, including bioinformatic analyses; implemented metabolomic analyses to identify metabolism-related signatures in urinary tract infections; refined the immunophenotyping of human bladder biopsies; and established a secure computing environment for data-driven analyses. By integrating these data and using differentiated computer models, a consistent picture of healthy urinary tracts and the changes caused by infections is to emerge. This forms the basis for precision medicine treatment approaches.

Groups involved

• Thomas M. Kessler: Neuro-Urology Balgrist ,University Hospital
• Onur Boyman: Department of Immunology, University of Zurich
• Martin Loessner: Department of Health Sciences and Technology, ETH Zurich
• Gunnar Rätsch: Department of Computer Science, ETH Zurich
• Shinichi Sunagawa: Department of Biology, ETH Zurich
• Emma Wetter Slack: Department of Health Sciences and Technology, ETH Zurich
• Nicola Zamboni: Department of Biology, ETH Zurich

Junior PIs

• André Kahles: Department of Computer Science, ETH Zurich
• Lorenz Leitner: Neuro-Urology Balgrist University Hospital and University of Zurich
• Enea Maffei: Department of Health Sciences and Technology, ETH Zurich
• Shawna McCallin: Neuro-Urology Balgrist University Hospital and University of Zurich
• Alaz Özcan: Center for Human Immunology, University of Zurich

Made possible by:

Monique Dornonville de la Cour-Foundation