Analysis of Pro- and Anti-Inflammatory Gene Response Patterns in Patients Receiving Phage Therapy

Phage therapy (PT) is a promising alternative for antibiotic-resistant infections, but its immunomodulatory effects in clinical settings remain poorly understood. This exploratory observational study aimed to characterize pro- and anti-inflammatory gene response patterns in ten patients undergoing personalized PT at the Phage Therapy Unit in Wrocław. Peripheral blood mononuclear cells (PBMCs) and granulocytes were analyzed to assess changes in the expression of 22 selected immune-related genes associated with innate and adaptive immune signaling pathways. While no uniform pattern of immune gene expression was observed across the cohort, individual cases exhibited significant up- or downregulation of specific genes. Interestingly, we identified biological age as a potential determinant of the host response. Specifically, older patients showed higher activation of the innate sensing machinery in PBMCs, characterized by a higher TLR4 fold change which may reflect the “inflammaging” phenomenon. These findings suggest that chronic exposure to bacterial viruses (bacteriophages), unlike many viral infections, does not trigger a predictable, significant systemic immune activation and that immune responses to PT are highly individualized by host- and phage-related biological factors. By documenting this spectrum of real-world responses, our work provides baseline data and hypotheses to guide the rational design of future preclinical and clinical investigations.