Editors' ChoiceINFLAMMATORY BOWEL DISEASE

Viruses storm the castle of IBD

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Science Translational Medicine  18 Feb 2015:
Vol. 7, Issue 275, pp. 275ec31
DOI: 10.1126/scitranslmed.aaa8320

As much as we like to be thought of as individuals, humans actually serve as homes to a vast array of organisms from at least three of the kingdoms of life: fungi, archaea, and bacteria, all of which make up the microbiota. However, our tenants are not limited to officially living things: viruses are also steady colonizers of the mammalian body. Much of the current work being performed on understanding the microbiota is focused on bacteria, and very little is known about how these other members influence human health. Indeed, bacteria are preyed upon by viral particles called bacteriophages that often outnumber the bacterial members of a given ecosystem by an order of magnitude. Thus, viruses, and specifically bacteriophages, within the gut represent a numerically prominent portion of the microbiota and as such have the potential to influence the dynamics of commensal bacterial communities.

Crohn's disease (CD) and ulcerative colitis (UC) are types of inflammatory bowel diseases (IBD) that arise from an inappropriate immune reaction to commensal bacteria in the gut. Individuals suffering from these diseases often have a dramatic loss in their intestinal bacterial diversity and alterations to the types of organisms present when compared to healthy individuals. To understand whether the commensal viruses, the virobiota, are also altered during IBD, Norman et al. isolated viral-like particle (VLP) preparations from individuals with either CD or UC, or healthy household controls. The use of household controls in this particular study is important, as recent evidence suggests that the microbiome is heavily influenced by the home environment such that people living together tend to have microbiotas that are more similar than individuals living apart. Thus, identification of organisms that might influence the course of disease might be more readily identified using household controls.

Because viruses require a host to replicate, it has been hypothesized that the bacteriophage community might mirror the dynamics of their bacterial host. However, Norman et al. found that this was not always the case. Using three cohorts of patients, from the UK, Los Angeles, and Chicago, the authors identified a consistent increase in the diversity of bacteriophages and expansion of one particular type of bacteriophage, Caudovirales, in people with IBD. More importantly, when bacterial and bacteriophage diversity were compared, they found an inverse correlation between Caudovirales diversity and bacterial richness. Therefore, expansion of these bacteriophages was not simply a result of increases in the bacterial hosts and suggests that bacteriophages might contribute to intestinal disease by changing the structure of the microbiota. A limitation of this study is that due to a paucity of annotated bacteriophages, the authors were unable to link specific phages to individual bacteria. Creating better databases will likely require a large-scale effort but will be necessary to fully understand how the virobiota influences disease. This study, however, emphasizes the complexity of the human microbiota and suggests that bacteria are not the only members of the microbiota that influence human health.

J. M. Norman et al., Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160, 1–14 (2015).[Abstract]

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