Temperate Phage Shape Honey Bee Gut Microbiome Structure and Response to Antibiotic Treatment

Authors

Sbardellati, D. L., Mehra, A., Ricigliano, V., Fine, J., Vannette, R.

Abstract

Bacteriophage (phage) are hypothesized to play a significant role in modulating gut microbiomes. Yet, in vivo research examining the role of phage in gut ecosystems remains sparse, largely due to a lack of tractable model systems. Here, we use the honey bee (Apis mellifera) gut as a model to test the hypotheses that phage-bacteria interactions in the gut are temporally variable and that stress, in the form of antibiotic application, can enhance phage killing of their bacterial hosts. First, we isolated and characterized a novel temperate phage which infects a bee-specific strain of Bifidobacterium. We then mono-colonized adult honey bees with this Bifidobacterium strain and tested how phage treatment impacts bacterial abundance over time. Next, using a series of in vitro and in vivo experiments, we examined how phage-bacteria interactions change in response to treatment with tetracycline, an antibiotic commonly used in commercial beekeeping. Finally, to probe the biological mechanisms underlying different phage-antibiotic synergies, we assayed how different classes of antibiotics impacted bacterial growth with and without phage infection. Our results indicate that temperate phage can promote the ability of Bifidobacterium to colonize the bee gut, while also increasing the adverse effect of tetracycline on Bifidobacterium abundance, suggesting that environmental stressors can shift phage-bacteria interactions from mutualism to antagonism. Additionally, our in vitro experiments show that phage-antibiotic synergy differ across antibiotic classes, suggesting that phage can synergize with different stressors in mechanistically distinct ways. Overall, this study highlights the significance of phage in shaping gut microbiomes, especially in response to antibiotic or xenobiotic exposure, thereby advancing our fundamental understanding of the factors which shape gut microbiomes.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 15 Jun 2026.

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