HUN-REN Biological Research Centre, Szeged 
Jul 14, 2026 | News
Researchers at the HUN-REN Biological Research Centre, Szeged are participating in a €15 million Horizon Europe programme that will investigate the combination of phage therapy and microbiome restoration in a European clinical trial. Recurrent urinary tract infections affect hundreds of millions of people worldwide, are particularly common among women, and in many cases require repeated courses of antibiotics. This not only reduces quality of life, but may also contribute to the spread of antibiotic-resistant bacteria and disrupt the healthy functioning of the gut microbiome. Researchers in the REPhRAME clinical trial, including Bálint Kintses and his group from Hungary, hope that the approach could help break the vicious cycle of recurrent urinary tract infections while sparing the gut microbiome.
Phage therapy and microbiome restoration in a single strategy
Recurrent urinary tract infections often do not end when the acute symptoms disappear. They may be driven by Escherichia coli strains that persist in the gut and later recolonize the urinary tract. Antibiotics can temporarily suppress these pathogens, but they may also damage beneficial members of the microbiome, which can contribute to further recurrences.
REPhRAME therefore targets both the current infection and one of its possible sources of recurrence. The first step of the treatment is a CRISPR-enhanced phage cocktail directed against pathogenic E. coli strains. Phages are viruses that infect bacteria and, when selected appropriately, can target the bacteria responsible for disease with high specificity. This is followed by INTESTIFIX001, a microbiome therapy developed by the Cologne Microbiota Bank, which aims to restore microbial balance in the gut and may help reduce the risk of further infections.
Testing the new approach in a European clinical trial
At the heart of REPhRAME is a multi-country, randomized, placebo-controlled Phase Ib/IIa clinical trial that will evaluate the safety, efficacy and clinical applicability of the treatment. Researchers will compare three approaches: phage therapy alone, phage therapy combined with antibiotics, and phage therapy followed by microbiome restoration.
The trial will not only ask whether phage therapy can reduce antibiotic use, but also in which patient groups, in what treatment sequence and under what microbiological conditions the approach may be most effective. Alongside clinical outcomes, researchers will collect microbiological, immunological and microbiome data to better understand the treatment’s mechanism of action and the conditions required for therapeutic success.
Szeged researchers focus on a key question in phage therapy
The Translational Microbiology Laboratory at HUN-REN BRC Szeged, led by Bálint Kintses, plays an important role in the project. The Szeged researchers contribute to the scientific foundation behind one of the central challenges in phage therapy: how to understand and predict which bacterial strains a given phage can effectively target.
Phages are highly specific. This is a major advantage, because it opens 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 of how this relationship may change during treatment.
The Szeged laboratory’s data-driven microbiological and phage therapy approaches may help move phage therapy beyond case-by-case experimental use toward a strategy that is predictable, measurable and clinically interpretable.
“The greatest promise of phage therapy lies in its specificity: when selected appropriately, phages can be directed against the bacterial strains causing the problem, without broadly disrupting bacterial communities. To achieve this, however, we need a precise understanding of the relationship between phages and bacteria. What makes REPhRAME particularly exciting is that this knowledge can now be applied as part of a major European clinical trial,” said Bálint Kintses, head of the Translational Microbiology Laboratory at HUN-REN BRC Szeged.
Phage therapy may enter a new stage of clinical development
REPhRAME is part of a broader European effort to turn bacteria-infecting phages into regulated, clinically validated treatment options for infections in which antibiotics are increasingly unable to provide durable solutions.
What makes the project distinctive is that it does not study phage therapy in isolation, but links it to microbiome restoration. This approach targets both the acute infection and the biological background that may contribute to recurrence. If successful, the clinical trial could help reduce antibiotic use, lower the number of recurrent infections and support the future integration of phage therapy into European clinical practice.
About the REPhRAME project
The REPhRAME project is coordinated by Universitätsmedizin Frankfurt. The consortium brings together 16 partners from academic, clinical, industrial, bioinformatics, drug development, regulatory and patient-centred research backgrounds. Partners include SNIPR Biome, Fraunhofer-Gesellschaft, the German Center for Infection Research, Hannover Medical School, University Hospital Cologne, HUN-REN Biological Research Centre, Szeged, Riga Stradiņš University, Leiden University Medical Center, Jafral, the Swiss Institute of Bioinformatics, the University of Bern, the University of Zurich, the University of Leicester and the University of Reading.
The project is funded by Horizon Europe and will run for five years. It will investigate how targeted antibacterial treatments can be combined with microbiome protection and restoration. In the longer term, the programme may contribute to reducing antibiotic use and to building the scientific and regulatory foundations for the clinical introduction of phage therapy.