Understanding Host–Phage Interactions in Chronic Wounds, Emphasising Inflammatory Markers and Neutralising Antibody Responses

Background Chronic wounds cause considerable morbidity, which is further compounded by antimicrobial resistance and biofilm formation. Bacteriophage therapy (BT) presents a promising alternative. However, issues such as host immune neutralisation and inflammatory reactions remain unresolved. Methods This prospective, interventional, non–randomized control study was conducted at the Institute of Medical Sciences, Banaras Hindu University, from July 2022 to February 2026. It involved 100 patients with chronic wounds (>6 weeks). It had two groups: Group I (n = 50) received bacteriophage therapy (BT), while Group II (n = 50) received conventional therapy (CT). Bacteriophages were isolated and applied topically every other day. Serum levels of IL-1β, IL-6, MMP-9, and TGF-β were measured using ELISA at baseline, immediately after therapy, and at six weeks after treatment completion. Neutralising antibodies in the BT group were measured through serum–phage interaction assays and data analysis was done. Results Follow-up was completed in 90% of patients. Diabetes (50%) was the most common comorbidity. The most commonly isolated bacteria were Pseudomonas aeruginosa (30%), Escherichia coli (26%), and Klebsiella pneumoniae (26%). The therapy duration was significantly shorter ( P < .001) in the BT group (1.46 ± 0.63 months) than in the CT group (2.92 ± 1.02 months). Levels of IL-1β, IL-6, MMP-9, and TGF-β decreased significantly in both groups during and after treatment. Neutralising antibodies were detected in only 2 out of 45 BT patients (4.4%) with complete follow-up. Conclusion BT promoted faster wound healing without notably altering cytokine profiles. The fact that around 4.4% of patients developed neutralising antibodies, which did not interfere with healing, suggests that phage therapy can be safely applied.