European project receives €15 million to study phage-based therapies

Bacteria are becoming increasingly resistant to antibiotics. One alternative is treatment with viruses that exclusively infect bacteria, known as phages. A research project funded by the European Union and led by Universitätsmedizin Frankfurt is the first to investigate, within the framework of a randomized clinical trial, the combination of phage therapy and restoration of the gut microbiome to prevent recurrent urinary tract infections.

Recurrent urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are becoming increasingly difficult to treat due to rising antibiotic resistance. An international research consortium coordinated by Universitätsmedizin Frankfurt is now pursuing a new approach. The project REPhRAME, led by Prof. Dr. Maria J.G.T. Vehreschild, has been awarded €15 million through the European research and innovation program Horizon Europe.

For the first time, a two-step therapeutic approach will be assessed in a randomized clinical trial. First, phages - viruses that specifically kill bacteria - will be used to combat the pathogens. This will be followed by restoration of the intestinal microbiome to prevent recurrent infections. The project began in June 2026 and is planned to run for five years.

Each year, more than 400 million people worldwide develop a urinary tract infection, and in 30 to 50 percent of cases the infection recurs. Since standard antibiotic treatment increases the risk of resistance, many patients find themselves trapped in a cycle of infection, antibiotic treatment, and reinfection, with no lasting solution.

Phage therapy is one of the most promising responses to the growing challenge posed by multidrug-resistant pathogens. The fact that Universitätsmedizin Frankfurt is leading this international consortium under the direction of Professor Vehreschild once again demonstrates our institution's outstanding role in translational infection research. I am confident that REPhRAME will significantly advance the clinical use of phage-based therapies - for the direct benefit of our patients."

Prof. Dr. Jürgen Graf, Medical Director and Chief Executive Officer of Universitätsmedizin Frankfurt

Prof. Dr. Enrico Schleiff, President of Goethe University, says: "By developing new therapies against bacterial pathogens, we are continuing the legacy of Paul Ehrlich, who discovered the first antibiotic in Frankfurt and thereby initiated medicine's successful fight against infectious diseases. Yet 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 and makes a significant contribution to strengthening Goethe University's research profile area Science for Health."

A new strategy to break the cycle of infection and antibiotic use

REPhRAME relies on phages because, unlike antibiotics, they act with a high degree of specificity: they attack only the target bacteria while leaving much of the natural microbiota unharmed.

The first treatment step uses SNIPR001, a phage cocktail developed using CRISPR gene-editing technology. It specifically targets the most common causes of urinary tract infections - certain strains of the intestinal bacterium Escherichia coli - while reducing the likelihood of new resistance emerging.

The second step focuses on restoring the gut microbiome. INTESTIFIX 001, a product of the Cologne Microbiota Bank, transfers stool bacteria from healthy donors to help re-establish the natural balance of the intestinal microbiota. The goal is to provide long-term protection against recurrent infections.

Clinical trial aims to pave the way for phage therapy in Europe

At the heart of the project is a multicenter clinical trial across Europe that will systematically evaluate the safety and effectiveness of the new treatment. Three approaches will be compared: phage therapy alone, phage therapy combined with antibiotics, and phage therapy followed by microbiome restoration

"Recurrent urinary tract infections place a substantial burden on patients and healthcare systems, yet existing treatment options are simply insufficient for many affected individuals," says Prof. Dr. Maria J.G.T. Vehreschild, Head of Infectious Diseases at Universitätsmedizin Frankfurt and overall coordinator of the project. "REPhRAME aims to transform phage therapy from a promising research concept into a clinically validated treatment option - with robust data on safety, efficacy, and implementation. In doing so, we hope to lay the foundation for integrating phage therapy into routine medical practice across Europe."

Frankfurt coordinates an international consortium

Led by Universitätsmedizin Frankfurt, the consortium brings together 16 partners from academia, clinical research, and industry across eight European countries. Together, they combine expertise in infectious diseases, clinical trials, phage therapy, microbiome research, microbiology, bioinformatics, regulatory science, drug development, and patient-centered research.

The partners include:

SNIPR Biome (Denmark)
Fraunhofer-Gesellschaft (Germany)
German Center for Infection Research (Germany)
Hannover Medical School (Germany)
LINQ management GmbH (Germany)
University Hospital Cologne (Germany)
HUN-REN Biological Research Centre (Hungary)
Riga Stradiņš University (Latvia)
Leiden University Medical Center (Netherlands)
Jafral (Slovenia)
Swiss Institute of Bioinformatics (Switzerland)
University of Bern (Switzerland)
University of Zurich (Switzerland)
University of Leicester (United Kingdom)
University of Reading (United Kingdom)

Research beyond the clinical trial

REPhRAME also includes a series of accompanying studies. These will examine how phages function and are broken down in the body, what immune responses they trigger, and how the microbiome changes throughout treatment.

In addition, the project will develop AI-based models to predict which patients are most likely to benefit from the therapy. Planned activities also include health-economic analyses and a systematic assessment of the patient perspective, including symptoms, quality of life, and acceptance of the new treatment.