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

Link to biorxiv: https://www.biorxiv.org/content/10.1101/2025.02.07.636470v2 To github: https://github.com/EpfeiferNutri/PrediRes Summary: The use of antibiotics disrupts the gut microbiota, potentially leading to long-term health issues and the spread of resistance. To investigate the impact of antibiotics on phage populations, we followed 22 healthy individuals two weeks before and up to six months after a three-day course of 3rd-generation cephalosporins. The populations of phages very rarely encoded antibiotic resistance genes and were mostly temperate including many phage-plasmids. Gut phages remained individual-specific even after microbiome perturbation by antibiotics. Yet, we found a 20% decline in phage diversity the day after treatment, alongside blooms of a few (mostly virulent) phages. We suggest that these temporary dominant phages contribute to the recovery of gut bacterial diversity through kill-the-winner dynamics. This is supported by the finding that several phages targeted Parabacteroides distasonis, a bacterium thriving after cephalosporin treatment, and which only proliferated when these phages were absent. Our findings suggest that phages play a crucial role in the gut microbiota's response to antibiotics by contributing to the restoration of microbial balance and diversity.