Recurrent phage treatment of Salmonella-infected chickens transiently reshapes gut microbiota composition and function

Bacteriophages (phages) are viruses that target bacteria and hold great promise as therapeutics against multidrug-resistant bacteria, pathogen infections, and for microbiota engineering. Despite their potential, the effect of phage therapy on gut microbiota remains insufficiently explored. This study investigated the impacts of recurrent phage administration on the gut microbiota of chickens challenged with Salmonella Enteritidis. Eighty chicks were infected at 7 days of age and either treated with a cocktail of six lytic phages of Salmonella via drinking water for 21 days before and after infection, or left untreated. Surprisingly, continuous high-dose phage treatment led to higher Salmonella colonization levels than short-term pre-infection exposure. Through fecal and cecal microbiota analysis, we found that phage treatment significantly influenced alpha and beta diversities as well as microbiota development, with the most significant changes occurring prior to Salmonella infection, and gradually diminishing over time. Furthermore, phage treatment transiently altered predicted microbiota functions, promoting an oxygen-utilizing microbial community that may have counteracted the protective effects of phages. These findings demonstrate that phages can induce time-dependent modifications in both the composition and functional profile of the gut microbiota, emphasizing the importance of considering these dynamic interactions when developing phage-based strategies against enteric pathogens.