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Review
, 9 (6)

The Human Gut Phage Community and Its Implications for Health and Disease

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Review

The Human Gut Phage Community and Its Implications for Health and Disease

Pilar Manrique et al. Viruses.

Abstract

In this review, we assess our current understanding of the role of bacteriophages infecting the human gut bacterial community in health and disease. In general, bacteriophages contribute to the structure of their microbial communities by driving host and viral diversification, bacterial evolution, and by expanding the functional diversity of ecosystems. Gut bacteriophages are an ensemble of unique and shared phages in individuals, which encompass temperate phages found predominately as prophage in gut bacteria (prophage reservoir) and lytic phages. In healthy individuals, only a small fraction of the prophage reservoir is activated and found as extracellular phages. Phage community dysbiosis is characterized by a shift in the activated prophage community or an increase of lytic phages, and has been correlated with disease, suggesting that a proper balance between lysis and lysogeny is needed to maintain health. Consequently, the concept of microbial dysbiosis might be extended to the phage component of the microbiome as well. Understanding the dynamics and mechanisms to restore balance after dysbiosis is an active area of research. The use of phage transplants to re-establish health suggests that phages can be used as disease treatment. Such advances represent milestones in our understanding of gut phages in human health and should fuel research on their role in health and disease.

Keywords: gut microbiome bacteriophages; gut microbiome phages; gut prophage reservoir; healthy gut phages.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Major factors influencing the structure, function, and dynamics of the gut phage community. Factors that can influence the phage community and serve as a source of phages are marked in thick black circles. Factors that only influence the viral community composition are marked in grey.
Figure 2
Figure 2
Schematic representation of the gut phage community development with age. Individuals are colonized early after birth, within 0–4 days after birth (DOB). During the first days of life, the diversity of the phage community is high and the microbial community abundance and diversity is low [51]. A reduction in Caudovirales diversity leads to an expansion and a shift in the microbial community composition and an increase in Microviridae phage diversity and abundance. A relatively stable phage community is maintained during the adult life. Changes in the phage community associated with a shift towards an elderly-like microbial community are unknown.
Figure 3
Figure 3
The adult gut phage community in health and disease. Bacteriophages found in human stool are an ensemble of lytic phages and activated prophages that arise from a larger prophage reservoir found in the gut microbial community. It has been proposed that the increase in phage diversity in inflammatory bowel disease patients comes from activation of a larger fraction of the prophage reservoir, which in turn leads to a decrease in bacterial diversity [11]. An increase of lytic phages has also been correlated with disease [60], suggesting that a proper balance between lytic phages and activated prophages is important to maintain health.
Figure 4
Figure 4
Bacteriophages in adult healthy individuals. The bacteriophage community of adult individuals is composed of members of the Caudovirales order, the Microviridae family and a large fraction of unclassified phages. Healthy individuals contained a relatively unique phageome and a set of shared phages between individuals that is globally distributed (<5% of total phageome). This set of shared phages has been correlated with health and proposed as the healthy gut phageome (HGP).
Figure 5
Figure 5
Phage community resilience and its contribution to the resilience of the bacterial community. A characteristic of a healthy microbiome is its ability to recover quickly from perturbations, after which a new “steady state” is established. Antibiotic administration results in profound changes in the microbial community, while changes in the viral community are only moderate. Phage–bacteria network interactions increase after perturbation and new networks are established in the new steady states. The phage component likely contributes to the recovery of the microbial community through the mobilization of beneficial genes.
Figure 6
Figure 6
Fecal microbial and the potential of viral filtrate transplant treatment to restore health. Fecal microbial transplants are considered a successful tool to treat certain microbiota-associated diseases and disorders [115,116,117,118,119,120,121,122,123,124,125,126,127]. Recently, a pilot study demonstrated that a transplantation of viral filtrates was sufficient to restore health in Clostridium difficile patients. This result highlights the potential for viruses to influence microbial communities, ultimately affecting health and disease.

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