Tracking gene flow in the gut microbiome reveals phage activation and host-range expansion in response to diet
Year: 2026
Type: preprint
Abstract: Horizontal gene transfer (HGT) drives microbial evolution, but what determines when genes move between species within complex communities remains unclear. We developed a junction-resolved metagenomic framework using short-read sequencing to distinguish mobile genetic element activation from de novo transfer and track both longitudinally. In a defined human gut community colonizing mice, mobile element activation was widespread but successful transfer was rare. A prophage carried by invading Phocaeicola vulgatus transferred reproducibly to resident species when the community resisted invasion, but not when dietary perturbation allowed the invader to expand. Transfer required prophage activation and persistence of a permissive recipient and coincided with diversification of a phage receptor-binding protein. Dietary polysaccharides reproduced prophage-associated fitness costs in vitro , and rhamnogalacturonan I induced cell lysis consistent with productive prophage activation. The framework also detected interspecies transfer retrospectively in longitudinal human metagenomes. Thus, diet and community ecology can redirect gene flow through the gut microbiome.
Language: English
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G4357913612, Programs on Critical Problems in Physics, Astrophysics and Biophysics at the Aspen Center for Physics, MIM: Systematic Dissection of Complex Synthetic Gut Bacterial Communities, A universal pipeline for functional characterization of the human microbiota at a massive scale, G8896167186, Illuminating the dark matter of the human small intestinal microbiota
OpenAlex ID: W7218607845