Researchers at the Hunlen Biology Research Center in Szeged are taking part in the €15 million Horizon Europe program to study the combination of phage therapy and microbiome recovery in European clinical trials. Recurrent urinary tract infections affect hundreds of millions of people worldwide, especially women, and often require repeated doses of antibiotics. This not only reduces quality of life, but also contributes to the spread of antibiotic-resistant bacteria and can disrupt the healthy functioning of the gut microbiome. Researchers at the REPhRAME clinical trial, including Hungary’s Barint Kintses and his group, hope that this approach will help break the cycle of recurrent urinary tract infections while preserving the gut microbiome.
Combining phage therapy and microbiome recovery into a single strategy
Recurrent urinary tract infections often persist even after the acute symptoms disappear. They can be driven by factors such as: Escherichia coli Strains that persist in the intestine and later recolonize the urinary tract. Although antibiotics can temporarily suppress these pathogens, they can also damage beneficial members of the microbiome, which can contribute to further recurrence.
Therefore, REPhRAME targets both the current infection and one possible cause of recurrence. The first step in treatment is a CRISPR-enhanced phage cocktail designed to target pathogenic cells. Escherichia coli Strain. Phages are viruses that infect bacteria, and when properly selected can attack disease-causing bacteria with high specificity. This is followed by INTESTIFIX001, a microbiome therapy developed by the Cologne Microbiome Bank. This aims to restore the balance of microorganisms in the gut and may help reduce the risk of further infections.
European clinical trial tests new approach
At the heart of REPhRAME is a randomized, placebo-controlled Phase Ib/IIa clinical trial in multiple countries that evaluates the safety, efficacy, and clinical applicability of the treatment. The researchers plan to compare three approaches: phage therapy alone, phage therapy plus antibiotics, and microbiome recovery after phage therapy.
The trial will ask not only whether phage therapy can reduce antibiotic use, but also in which patient groups, in what sequence of treatments, and under what microbiological conditions the approach is most effective. Researchers will collect microbiological, immunological and microbiome data alongside clinical results to better understand the treatment’s mechanism of action and the conditions necessary for its success.
Szeged researchers focus on key questions in phage therapy
The Translational Microbiology Laboratory at HUN-REN BRC Szeged, led by Bálint Kintses, plays a key role in this project. Szeged researchers are contributing to the scientific foundation behind one of the central challenges in phage therapy: how to understand and predict which bacterial strains a particular phage can effectively target.
Phages are very specific. This is a major advantage as it opens up the possibility of targeting pathogenic bacteria more precisely than broad-spectrum antibiotics. At the same time, this specificity is also a challenge. Successful phage therapy requires a detailed understanding of the relationship between phages and bacteria and how this relationship changes during treatment.
The Szeged Institute’s data-driven microbiological and phage therapy approach could help move phage therapy beyond case-by-case experimental use to a predictable, measurable, and clinically interpretable strategy.
“The greatest promise of phage therapy lies in its specificity. If chosen appropriately, phages can be targeted at the bacterial strain causing the problem without broadly disrupting the bacterial community. However, to achieve this, we need to understand precisely the relationship between phages and bacteria. What makes REPhRAME particularly interesting is that this knowledge can be applied as part of a major clinical trial in Europe.” Balint Kintses, Head of the Translational Microbiology Laboratory at Hunlen BRC Szeged, said:
Phage therapy could enter a new phase of clinical development
REPhRAME is part of a broader European effort to transform phages, which infect bacteria, into a regulated, clinically-validated treatment option for infections where antibiotics are no longer providing a durable solution.
What is unique about this project is that it does not study phage therapy in isolation, but links it with microbiome recovery. This approach targets both the acute infection and the biological background that may contribute to relapse. If successful, this clinical trial could reduce the use of antibiotics, reduce the number of recurrent infections, and support the integration of phage therapy into future European clinical practice.
About the REPhRAME project
The REPhRAME project is coordinated by the Frankfurt Medical University. The consortium brings together 16 partners with academic, clinical, industrial, bioinformatics, drug development, regulatory and patient-centered research backgrounds. Partners include SNIPR Biome, Fraunhofer-Gesellschaft, German Center for Infectious Diseases Research, Hannover Medical School, Cologne University Hospital, Hunlen Biological Research Center, Szeged, Riga Stradis University, Leiden University Medical Center, Jafrar, Swiss Institute for Bioinformatics, University of Bern, University of Zurich, University of Leicester and University of Reading.
The project is funded by Horizon Europe and will run for five years. We investigate how targeted antimicrobial treatments can be combined with microbiome protection and restoration. In the long term, this program may reduce the use of antibiotics and contribute to building the scientific and regulatory infrastructure for the clinical introduction of phage therapy.
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Hunlen Biology Research Center in Szeged
