Researchers at the HUN-REN Biological Research Centre, Szeged are participating in a €15 million Horizon Europe program that will investigate the combination of phage therapy and microbiome restoration in a European clinical trial, according to a Jul. 14 announcement. The REPhRAME project aims to address recurrent urinary tract infections, which affect hundreds of millions worldwide and often require repeated antibiotic courses.
The REPhRAME clinical trial involves researchers such as Bálint Kintses and his group from Hungary. They hope their approach could help break the cycle of recurring infections while preserving gut health. "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.
Recurrent urinary tract infections are often caused by Escherichia coli strains that persist in the gut and recolonize the urinary tract after initial symptoms subside. While antibiotics may suppress these pathogens temporarily, they can also damage beneficial microbes in the gut microbiome and contribute to further recurrences.
The treatment under investigation begins with a CRISPR-enhanced phage cocktail targeting pathogenic E. coli strains. This is followed by INTESTIFIX001—a microbiome therapy developed by Cologne Microbiota Bank—designed to restore microbial balance in the gut and potentially reduce future infection risk.
REPhRAME’s multi-country Phase Ib/IIa randomized placebo-controlled trial will compare three approaches: phage therapy alone; phage therapy combined with antibiotics; and phage therapy followed by microbiome restoration. Researchers will evaluate safety, efficacy, patient groups most likely to benefit, treatment sequences, and underlying microbiological conditions.
Coordinated by Universitätsmedizin Frankfurt with 16 partners across academia, industry, bioinformatics, drug development and regulatory sectors—including institutions from Germany, Hungary, Latvia, Switzerland, Netherlands and United Kingdom—the five-year project seeks not only to reduce antibiotic use but also build scientific foundations for regulated clinical adoption of targeted antibacterial treatments.
