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Published on: January 5, 2024
Species-specific prophage induction by ciprofloxacin in human gut metagenomes
Ben Sakdinan1, Anshul Sinha2, Firdausi Qadri3
1Department of Microbiology & Immunology, McGill University, Montréal, QC, Canada.
Abstract:
Antibiotics are known to trigger prophage induction in controlled laboratory settings, but it remains unclear whether this also occurs within microbiomes in nature. Current methods investigating the link between antibiotics and prophage induction within the human gut rely on in vitro culturing of human gut bacterial isolates. Using a metagenomic approach, we aimed to measure prophage induction and whether it is associated with antibiotic exposure. Across two independent human cohorts, we compared prophage to bacterial host read depth ratios (P:H) across known or measured antibiotic exposures. We found that induction is not broadly associated with antibiotic exposures at the level of the overall microbiome, but that ciprofloxacin increases P:H ratios in specific bacterial species. We documented heterogeneous trajectories of P:H ratios over the course of antibiotic exposure, sometimes increasing and remaining high, or returning to baseline. This study complements experimental models by providing in vivo evidence of induction in the human gut.
Insights
Antibiotic exposure does not broadly induce prophages in the human gut microbiome. However, ciprofloxacin specifically increases phage induction in certain bacterial species, showing varied responses over time.
Area of Science:
- Microbiology and Virology
- Human Microbiome Research
- Antibiotic Resistance and Phage Interactions
Background:
- Bacteriophages (phages) are viruses that infect bacteria, with two life cycles: lytic and lysogenic.
- In the lysogenic cycle, phages integrate as prophages into the bacterial genome.
- Prophage induction, a switch to the lytic cycle, leads to host cell lysis and viral particle release.
Purpose of the Study:
- To investigate whether antibiotic exposure triggers prophage induction within the human gut microbiome.
- To assess the association between antibiotic exposure and prophage induction using a metagenomic approach.
- To provide in vivo evidence of prophage induction in the human gut, complementing in vitro studies.
Main Methods:
- Utilized a metagenomic approach to analyze samples from two independent human cohorts.
- Compared prophage to bacterial host read depth ratios (P:H) in relation to antibiotic exposure.
- Examined P:H ratios across different bacterial species and over the course of antibiotic treatment.
Main Results:
- Prophage induction was not broadly associated with antibiotic exposures at the overall microbiome level.
- Ciprofloxacin exposure was found to increase P:H ratios in specific bacterial species.
- Observed heterogeneous trajectories of P:H ratios during antibiotic exposure, with some remaining high and others returning to baseline.
Conclusions:
- Antibiotic-induced prophage induction is not a widespread phenomenon in the human gut microbiome.
- Specific antibiotics, like ciprofloxacin, can induce prophages in particular bacterial species in vivo.
- The study provides crucial in vivo evidence of phage induction in the human gut, highlighting species-specific effects and dynamic responses.
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