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A Theoretical Model of Temperate Phages as Mediators of Gut Microbiome Dysbiosis

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Review

A Theoretical Model of Temperate Phages as Mediators of Gut Microbiome Dysbiosis

Derek M Lin et al. F1000Res.

Abstract

Bacteriophages are the most prominent members of the gut microbiome, outnumbering their bacterial hosts by a factor of 10. Phages are bacteria-specific viruses that are gaining attention as highly influential regulators of the gut bacterial community. Dysregulation of the gut bacterial community contributes to dysbiosis, a microbiome disorder characterized by compositional and functional changes that contribute to disease. A role for phages in gut microbiome dysbiosis is emerging with evidence that the gut phage community is altered in dysbiosis-associated disorders such as colorectal cancer and inflammatory bowel disease. Several recent studies have linked successful fecal microbiota transplantation to uptake of the donor's gut phage community, offering some insight into why some recipients respond to treatment whereas others do not. Here, we review the literature supporting a role for phages in mediating the gut bacterial community, giving special attention to Western diet dysbiosis as a case study to demonstrate a theoretical phage-based mechanism for the establishment and maintenance of dysbiosis.

Keywords: Bacteriophage; dysbiosis; fecal microbiota transplant; gut; microbiome; phage; prophage-encoded genes; virome; western diet.

Conflict of interest statement

Competing interests: The authors have intellectual property rights in areas related to bacteriophages and gut microbiome dysbiosis. No competing interests were disclosed.No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Reproductive life cycles of a temperate phage.
Temperate phages can reproduce via both lytic and lysogenic cycles. The decision as to which cycle gets induced depends on environmental factors. This simplified version of phage life cycles demonstrates how the cycles are intertwined.
Figure 2.
Figure 2.. Theoretical model for phage-mediated dysbiosis.
Prophages can drive otherwise commensal bacterial hosts (symbionts) to behave pathogenically (pathobionts) when exposed to environmental stressors, such as those associated with a Western diet. Phage-encoded genes support bacterial mechanisms for bacterial survival at the cost of the human host. The pathogenic behavior of these resident gut microbes promotes inflammation in the intestinal epithelium, which perpetuates the state of environmental stress and persistent dysbiosis.

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Grant support

This study was supported in part by the Winkler Bacterial Overgrowth Research Fund.

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