Bacteria are becoming increasingly resistant to antibiotics. One alternative is treatment with viruses that infect only bacteria, known as phages. A research project funded by the European Union and led by the University of Frankfurt is the first to investigate the combination of phage therapy and gut microbiota restoration to prevent recurrent urinary tract infections within the framework of a randomized clinical trial.
Recurrent urinary tract infections (UTIs) are one of the most common bacterial infections worldwide and are becoming increasingly difficult to treat due to rising antibiotic resistance. An international research consortium coordinated by Frankfurt Medical University is currently pursuing a new approach. The project REPhRAME, led by Professor Maria JGT Vehreschild, has been awarded €15 million through the European research and innovation program Horizon Europe.
For the first time, a two-step treatment approach will be evaluated in a randomized clinical trial. First, phages, which are viruses that specifically kill bacteria, are used to fight pathogens. It then restores the gut microbiome and prevents infections from recurring. The project is scheduled to begin in June 2026 and run for five years.
Each year, more than 400 million people worldwide develop a urinary tract infection, and 30-50% of these infections recur. Because standard antibiotic treatment increases the risk of resistance, many patients are trapped in a cycle of infection, antibiotic treatment, and reinfection with no permanent solution.
Phage therapy is one of the most promising responses to the growing challenges posed by multidrug-resistant pathogens. The fact that the University of Frankfurt is leading this international consortium under the direction of Professor Wereschild once again confirms our institution’s outstanding role in translational infection research. I am confident that REPhRAME will significantly advance the clinical use of phage-based therapeutics for the direct benefit of patients. ”
Professor Jürgen Graf, Medical Director and CEO, Faculty of Medicine, University of Frankfurt
Professor Enrico Schleiff, Rector of Goethe University, said: “By developing new treatments against bacterial pathogens, we owe a debt to Paul Ehrlich, who discovered the first antibiotic in Frankfurt and thereby brought about the success of medicine in the fight against infectious diseases. Continuing the legacy. However, biology never stands still, and in the face of increasing bacterial resistance, Goethe University is vigorously pursuing new holistic treatment concepts. REPhRAME is an excellent example of this strategy. He has made a significant contribution to strengthening Goethe University’s research profile in the field of health sciences. ”
New strategies to break the cycle of infections and antibiotic use
REPhRAME relies on phages because, unlike antibiotics, phages act with high specificity. Phages attack only the target bacteria while leaving most of the natural microbiome intact.
The first processing step uses SNIPR001, a phage cocktail developed using CRISPR gene editing technology. It specifically targets specific strains of the enteric bacterium E. coli, the most common cause of urinary tract infections, reducing the chance of new resistance emerging.
The second step focuses on restoring the gut microbiome. INTESTIFIX 001, a product of the Cologne Microbiome Bank, helps to re-establish the natural balance of the gut microbiome by transplanting fecal bacteria from a healthy donor. The goal is long-term protection from recurrent infections.
Clinical trial aims to pave the way for phage therapy in Europe
At the heart of this project is a multicenter clinical trial across Europe that systematically evaluates the safety and efficacy of new treatments. Three approaches are compared: phage therapy alone, phage therapy in combination with antibiotics, and microbiome recovery after phage therapy.
“Recurrent urinary tract infections place a huge burden on patients and the healthcare system, but for many affected people, existing treatment options are completely inadequate,” says Professor Maria JGT Wehreschild, Head of the Department of Infectious Diseases at the University of Frankfurt and overall coordinator of the project. “REPhRAME aims to transform phage therapy from a promising research concept into a clinically validated treatment option, backed by solid data on safety, efficacy and implementation. In doing so, we hope to lay the foundation for the integration of phage therapy into daily medical practice across Europe.”
Frankfurt coordinates international consortium
Led by the University of Frankfurt, the consortium brings together 16 partners from academia, clinical research and industry from eight European countries. They combine expertise in infectious diseases, clinical trials, phage therapy, microbiome research, microbiology, bioinformatics, regulatory science, drug development, and patient-centered research.
Partners include:
SNIPR biome (Denmark)
Fraunhofer Society (Germany)
German Center for Infectious Disease Research (Germany)
Hannover Medical University (Germany)
LINQ Management GmbH (Germany)
Cologne University Hospital (Germany)
Hunlen Biological Research Center (Hungary)
Riga Stradis University (Latvia)
Leiden University Medical Center (Netherlands)
Jafrar (Slovenia)
Swiss Bioinformatics Institute (Switzerland)
University of Bern (Switzerland)
University of Zurich (Switzerland)
University of Leicester (UK)
University of Reading (UK)
Research beyond clinical trials
REPhRAME also includes a series of companion studies. These investigate how phages function and are broken down in the body, what immune responses they provoke, and how the microbiome changes during treatment.
Additionally, the project will develop an AI-based model to predict which patients are most likely to benefit from treatment. Planned activities will also include health economic analysis and systematic evaluation from the patient’s perspective, including symptoms, quality of life, and acceptance of new treatments.
sauce:
Goethe University Frankfurt am Main
