Antibiotic perturbation of the human gut phageome preserves its individuality and promotes blooms of virulent phages

Abstract

Antibiotic use disrupts the gut microbiota, posing risks of long-term health issues and resistance. To study its impact on gut phages, we followed 22 healthy individuals 2 weeks before and up to 6 months after a 3-day course of 3^rd-generation cephalosporins. Our results show that gut phages rarely encode antibiotic resistance genes and are mostly temperate, including many phage plasmids. Furthermore, phage populations remain individual-specific even after microbiome perturbation. Yet, we report a 20% decline in phage diversity the day after treatment, alongside blooms of a few, mostly virulent, phages. We suggest that some of these phages contribute to the recovery of bacterial diversity via "kill-the-winner" dynamics. This is supported by (temporarily) dominant phages targeting Parabacteroides distasonis, a bacterium that thrives post-treatment only in the absence of these phages. Our findings suggest gut phages are crucial to the microbiome response to antibiotics, aiding the restoration of balance and diversity.

Keywords: CP: Microbiology; antibiotics; cephalosporin; gut perturbation; gut phageome; healthy individuals; human gut microbiota; kill-the-winner; metagenomics; phage-plasmid; viromics.