Phage therapy: from case-based translational research to Gut-On-A-Chip model of digestive decolonization

Antimicrobial resistance and more specifically bacterial resistance to antibiotics is a global threat for human health, and its burden is only expected to steadily increase in the coming decades. Complementary therapeutic tools are thus urgently needed in the fight against infections caused drug-resistant bacteria. Among them, phage therapy, the therapeutic use of lytic bacteriophage viruses, is likely the one to generate the most interest in recent clinical and fundamental research. In this work, we related the use of phage therapy in seven patients who varied significantly in terms of demographical characteristics, clinical indication, phage therapy administration routes and outcomes. Through "reverse translational research", going from bedside to bench, we attempted to further characterize the factors likely to influence therapeutic success or failure. We suggested that complex mechanisms lying at different intersections between phages, antibiotics, bacteria and human patients might play crucial roles in that regard. We also investigated the "carriage-infection conversion" paradigm of bacterial infections happening in the early post-operative period of pediatric liver transplantation recipients. This was allowed by a prospective study monitoring over 40 children awaiting liver transplantation, and by the use of a complex three-dimensional in-flow cell culture model, the Gut-On-A-Chip, to obtain preliminary insight in the potential of phage therapy to selectively decolonize the digestive carriage of specific bacterial species.