The effects of bacteriophage cocktail treatment on healthy gut microbiota: an in vitro human colon model study

The human gut microbiome is a complex community that plays an important role in health, where perturbations can result in dysbiosis and disease. Bacteriophages (phages) can provide treatment for bacterial gastrointestinal disease, and commercial preparations such as the Intesti bacteriophage cocktail can be taken orally to target bacterial pathogens. However, interactions between these phages and the native gut microbiota are understudied. To investigate the impact of phage treatment, we used simulated gut models seeded with healthy donor microbiota from three individuals, sequenced the DNA and analysed the bacterial and viral portions from samples obtained over time. Each donor had a unique bacterial composition that diverged with time. When comparing phage-treated to control samples, we observed that Escherichia coli abundance accounted for the largest portion of bacterial community variance and was more associated with the controls. The lower abundance in phage-treated samples may have resulted from the lytic action of phages from the cocktail. Additionally, our analyses of the viral portion revealed a phage bloom exclusive to phage-treated samples. A highly abundant phage in this bloom was matched with the Intesti bacteriophage cocktail, showed similarity to Enterobacteria phage phi92 and provided evidence of productive infection within the model. While we did observe fluctuations in relative abundance of additional viral sequences in the presence of the phage cocktail, these changes were often transient. Furthermore, we detected only slight differences from typical members of the virome and low numbers of active prophages. Our experiments suggest that the phage cocktail had minimal interruption to the native gut microbiota within the model.