Abundance measurements reveal the balance between lysis and lysogeny in the human gut microbiome

• Published in: Current biology Vol. 35; no. 10; pp. 2282 - 2294.e11
• Main Authors: Lopez, Jamie Alcira, McKeithen-Mead, Saria, Shi, Handuo, Nguyen, Taylor H., Huang, Kerwyn Casey, Good, Benjamin H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 19.05.2025
• Subjects: Animals; Bacteria - genetics; Bacteria - virology; bacteriophage; Bacteriophages - genetics; Bacteriophages - physiology; Gastrointestinal Microbiome - physiology; gut microbiome; Humans; induction; Lysogeny; mathematical modeling; metagenomics; Mice; microbial ecology; population dynamics; Virome; virus; virus-to-microbe ratio; virome; gut microbiome; induction; metagenomics; mathematical modeling; microbial ecology; bacteriophage; virus; virus-to-microbe ratio; population dynamics
• ISSN: 0960-9822; 1879-0445; 1879-0445
• DOI: 10.1016/j.cub.2025.03.073

The human gut contains diverse communities of bacteriophage, whose interactions with the broader microbiome and potential roles in human health are only beginning to be uncovered. Here, we combine multiple types of data to quantitatively estimate gut phage population dynamics and lifestyle characteristics in human subjects. Unifying results from previous studies, we show that an average human gut contains a low ratio of phage particles to bacterial cells (∼1:100) but a much larger ratio of phage genomes to bacterial genomes (∼4:1), implying that most gut phage are effectively temperate (e.g., integrated prophage and phage-plasmids). By integrating imaging and sequencing data with a generalized model of temperate phage dynamics, we estimate that phage induction and lysis occur at a low average rate (∼0.001–0.01 per bacterium per day), imposing only a modest fitness burden on their bacterial hosts. Consistent with these estimates, we find that the phage composition of a diverse synthetic community in gnotobiotic mice can be quantitatively predicted from bacterial abundances alone while still exhibiting phage diversity comparable to native human microbiomes. These results provide a foundation for interpreting existing and future studies on links between the gut virome and human health. [Display omitted] •The human gut contains a high density of phage genomes but few phage particles•Most gut phage utilize a temperate or otherwise host-associated lifestyle•Phage induction occurs at a low frequency, implying a low fitness cost to bacteria•Current computational methods overestimate the prevalence of lytic gut phage Lopez et al. combine multiple classes of data and mathematical modeling to provide a quantitative view of gut virome ecology. They find an ecosystem dominated largely by quiescent phage that exist within host bacteria, in strong contrast to more lytic ecosystems such as the surface ocean.