The human gut is home to dense bacterial and phage populations that are involved in regulating human health.
Phages regulate bacterial abundance, diversity and metabolism in numerous ecosystems, but their effects in the human gut remain largely unexplored.
Despite high bacterial abundance and metabolism, the majority of described phages in the gut are integrated within their bacterial hosts, which suggests dynamic interactions that are specific to this system.
Different bacteria–phage interactions occur depending on the health status and development stage of the human host. Characterization of these interactions would provide unique ways to improve disease or developmental outcomes.
Further research on phage replication cycles and phage pharmacodynamics is essential before considering their therapeutic use for human health.
The human gut is host to one of the densest microbial communities known, the gut microbiota, which contains bacteria, archaea, viruses, fungi and other microbial eukaryotes. Bacteriophages in the gut are largely unexplored, despite their potential to regulate bacterial communities and thus human health. In addition to helping us understand gut homeostasis, applying an ecological perspective to the study of bacterial and phage communities in the gut will help us to understand how this microbial system functions. For example, temporal studies of bacteria, phages and host immune cells in the gut during health and disease could provide key information about disease development and inform therapeutic treatments, whereas understanding the regulation of the replication cycles of phages could help harness the gut microbiota to improve disease outcomes. As the most abundant biological entities in our gut, we must consider bacteriophages in our pursuit of personalized medicine.
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This work was supported by the Canada Research Chair Program and the Bill and Melinda Gates Foundation (OPP1139814). The authors thank members of the Maurice laboratory and E. Haggård-ljungquist for constructive comments on this manuscript.
The authors declare no competing financial interests.
The collective genomes of all microorganisms in an ecosystem.
The collection of all microorganisms that exist in an ecosystem.
Chemical substances that are foreign to an ecosystem.
An imbalance in microbial diversity that is usually characterized by a decrease in specific members of the Firmicutes and an increase in members of the Proteobacteria.
- Genome annotation
The process of identifying, characterizing and annotating all coding and non-coding regions in a genome.
- Cryptic phages
Defective prophages that lack the ability to return to the lytic cycle.
(KTW). A specific case of Lotka–Volterra dynamics that is applied to bacterial and phage communities. The KTW hypothesis models the frequency-dependent viral infection of temporally abundant and active bacterial taxa, allowing for high bacterial diversity.
(R–M). A bacterial defence system against invading foreign unmethylated DNA; for example, from phages and plasmids. Unmethylated DNA sites are recognized and cleaved by specific bacterial restriction endonucleases.
- Selective sweeps
The reduction or elimination of genetic variation in regions linked to a recently fixed beneficial mutation that increases host fitness.
- Fluctuating selection dynamics
A model of co-evolutionary dynamics that is characterized by the fluctuation of the selection pressure on genes, phenotypes or species in variable environments over time. In this model, there is maintenance of within-population genetic diversity over time, with variants that might become advantageous under appropriate environmental conditions.
- Piggyback-the-winner model
A recent model of bacteria–phage interactions, whereby phages integrate as prophages and undergo the lysogenic replication cycle instead of the lytic cycle when bacterial density and activity increase.
- Abortive infection system
(Abi system). Phage infection that leads to bacterial death and loss of the phage genome, without the production of any phages.
- Competitive exclusion
A mechanism whereby two (or more) related species that are competing for the same resources cannot stably coexist in the same environment and must specialize.
- Quorum sensing
A system of bacteria-produced molecular stimuli and responses that coordinate bacterial gene expression (of genes that are involved in biofilm formation, virulence and antibiotic resistance), according to the local density of the bacterial population.
- Gnotobiotic mice
Germ-free mice or antibiotic-treated mice that are colonized with predefined bacterial species or communities.
- Chronic otitis
A term that is used to describe various symptoms that result from the long-term damage of the middle ear by infection and inflammation.
The study of the effects and mechanisms of action of a compound (typically therapeutic drugs) on a living organism.
The study of the absorption, distribution, metabolism and excretion of a compound, typically applied to the study of therapeutic drugs.
- Temperate phages
Phages that replicate through lysogenic or lytic replication.
- Latency period
The time between phage infection and bacterial lysis with the release of new progeny.
- Burst size
The number of progeny produced per infecting phage.
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Mirzaei, M., Maurice, C. Ménage à trois in the human gut: interactions between host, bacteria and phages. Nat Rev Microbiol 15, 397–408 (2017). https://doi.org/10.1038/nrmicro.2017.30
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