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

PFEIFER, E.; Humieres, C.; Lamy-Besnier, Q.; Plaza-Onate, F.; Denise, R.; Dion, S.; Condamine, B.; Touchon, M.; Ma, L.; Burdet, C.; Mentre, F.; Denamur, E.; Rocha, E.

doi:10.1101/2025.02.07.636470

bioRxiv · 10.1101/2025.02.07.636470

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

PFEIFER, E.·Humieres, C.·Lamy-Besnier, Q.·Plaza-Onate, F.·Denise, R.·Dion, S.·Condamine, B.·Touchon, M.·Ma, L.·Burdet, C.·Mentre, F.·Denamur, E.·Rocha, E.

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Abstract

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 microbiotas response to antibiotics by contributing to the restoration of microbial balance and diversity. HighlightsO_LIIn healthy individuals, cephalosporin antibiotics cause an approx. 20% decline in gut phage richness that is restored after 30 days C_LIO_LIHuman gut phage communities are specific of each individual, which is retained post-antibiotic treatment C_LIO_LIAntibiotic perturbation causes an increase in the number of dominant virulent phages supporting kill-the-winner dynamics as mechanisms for shaping bacterial diversity C_LIO_LIDominance of Parabacteroides distasonis (after cephalosporin treatment) is likely disrupted through its specific phages C_LI eTOCAntibiotic-induced disruption of the gut microbiome leads to a transient loss of microbiome diversity (bacterial and viral) and causes blooms of bacteria and their viruses. Our analysis suggests that these viruses prey on dominant bacteria, prevent their dominance, and contribute to the recovery of microbiome balance. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=96 SRC="FIGDIR/small/636470v2_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@98c366org.highwire.dtl.DTLVardef@1446921org.highwire.dtl.DTLVardef@51f941org.highwire.dtl.DTLVardef@1c328ed_HPS_FORMAT_FIGEXP M_FIG C_FIG

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PFEIFER, E., Humieres, C., Lamy-Besnier, Q., Plaza-Onate, F., Denise, R., Dion, S., Condamine, B., Touchon, M., Ma, L., Burdet, C., Mentre, F., Denamur, E., Rocha, E.. 2025-02-08. Third-generation cephalosporin antibiotics induce phage bursts in the human gut microbiome.. https://doi.org/10.1101/2025.02.07.636470

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