Third-generation cephalosporin antibiotics induce phage bursts in the human gut microbiome

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 3 ^rd -generation cephalosporins. The populations of phages encoded very rarely 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 and abundance the day after treatment, caused by the burst of a few (mostly virulent) phages. We suggest they contribute to the recovery of gut bacterial diversity, since several targeted Parabacteroides distasonis , a bacterium thriving after cephalosporin treatment that only proliferated in the absence of these phages. Our findings point out that phages play a crucial role in the gut microbiota’s response to antibiotics by restoring microbial balance and diversity.