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.
Selected research findings
Validated procedures are required for clinical studies to ensure the reliable collection, preparation, and analysis of samples. These procedures were optimized in the course of the mTORUS project to ensure the quality and reproducibility of the results.
Examination of the bladder microbiome
For these validation studies, samples were collected from 66 patients in order to analyze the microbiome and metabolome, as well as to cultivate and produce bacterial cultures. Initial results show that the bladder microbiome varies considerably across the patient population. In addition, the choice of preparation method (buffer medium) influences the composition of the bacterial populations (graphic). It is therefore crucial for the project to define standardized processes and conditions in order to ensure optimal reproducibility of the results.
Urine samples for metabolomic analyses
The processing of urine samples for the determination of the metabolome was also improved, particularly with regard to the normalization of urine concentration and the sensitivity in detecting metabolites at low concentrations. These improvements are essential for better capturing the metabolic effects of a urinary tract infection.
Investigation of immunological responses
The effects of urinary tract infections on the immune system were measured using flow cytometry-based immunophenotyping. In an initial study, 14 bladder biopsies were analyzed, divided into two patient groups (with and without urinary tract infection). Preliminary results indicate a type III immune response, which typically occurs with extracellular bacteria or fungi. These findings will be further explored in follow-up studies.
For the detailed analysis of the collected multidimensional data (clinical status, microbiome, metabolome, immune status), a secure computing environment was established. Currently, methods for data integration and computer based models are being developed in order to better understand the changes in biological parameters resulting from urinary tract infections.
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
Tailored treatment of urinary tract infections
↑ Interview with Prof. Kessler (in German)
Project Overview
Lead:
Prof. Dr. Thomas M. Kessler
Head Physician Neuro-Urology University Clinic Balgrist
Ordinarius Neuro-Urology University of Zurich
Duration: 2023 – 2028
Universities: ETH Zürich, University of Zurich
Hospitals: University Clinic Balgrist, University Hospital Zurich
Researchers: 25
Partner: EPFL
Patients: 375