A New Look At Irritable Bowel Disease and Viruses: The Core Human "Phageome"

An illustration of the core protein clusters (PCs; groups
of similar genes) found in the photic and aphotic zones
of the ocean. This new study applies a similar approach
using phage genomes instead of genes. Source

Ongoing research has continued to implicate the microbiome in a variety of human diseases. We often hear about this in the context of bacterial communities. Certain bacterial communities appear to be associated with health, and disrupting these communities seems to be associated with disease. To better understand these bacterial communities, we sometimes group the shared members together as the "core bacterial community" that is associated with health or disease. In some ways these core bacteria are considered important to the system because they are found in every instance of health or disease. But what about the core phages (bacterial viruses) of these communities? A few weeks ago Manrique et al published a study that began addressing this question.

Manrique et al published a study in PNAS that looked at the core human "phageome" in health and disease. The goal of the study was to identify the core set of phages that are part of the human gut phageome and observe how they are changed in disease states. The purpose of this study is ultimately to identify those phages that are likely to play roles in maintaining health by identifying phages that are present in health and absent in disease. Overall I liked this paper and I will leave you to read it yourself for the study specifics. Here I just want us to briefly summarize the paper while highlighting the most important points.

The group began by assembling a small human cohort consisting of two subjects whose stool was sampled at two different time points. They purified the viruses out of the stool and sequenced the genomic DNA using whole genome shotgun sequencing. They combined the sequences from the four samples and used them to assemble approximately 4,000 contigs. As was expected, they identified a core set of phages that were present in all of the samples.

This was interesting, but what really made the paper cool was the expansion of their methods to a more robust, disease-associated virome dataset. The group performed their analysis on the Norman et al virome dataset, which includes purified virus (mostly phage) genomic DNA from the stool of healthy subjects, as well as subjects suffering from irritable bowel disease conditions. This dataset allowed the group to investigate how the core phage communities differed between healthy and diseased (IBD) states. The geographic diversity of the sampling also allowed them to account for location variation in the core virome.

Heatmap of the core, common, and unique phage
genomes found in the Manrique et al study.

The takeaway points were as follows:

• A core gut virome exists.
• The core gut virome is conserved across geographically distant populations.
• The core gut virome signatures change in disease states.
• Sequence homology clustering reduces core virome dimensionality while preserving population signatures.

In the end, what does this all mean? I think the biggest strength of this paper is that they are laying important groundwork for future studies of the human virome in the context of the "core virome". By identifying those phages present in all healthy states, the group has identified targets for future study that are likely to be important for a healthy system. This also establishes a new way for other researchers to start thinking about the viromes in their systems of interest.

So what's next? Here are my predictions for the future directions of this study:

• The group will likely expand to additional body sites and disease states.
• The group may go on to define the functional and predatory implications of core virome.
• They or others will begin establishing an understanding of the associations between the core virome and the core bacterial communities.

Again, this is a cool paper and I suggest you check it out. I also presented this paper for our lab journal club a couple of weeks ago, and I made my slide deck available here if you want to check it out. Finally, and as always, feel free to reach out either in the comments below, on Twitter, or by email. I am always excited to hear from my readers!

Works Cited

Manrique P, Bolduc B, Walk ST, van der Oost J, de Vos WM, & Young MJ (2016). Healthy human gut phageome. Proceedings of the National Academy of Sciences of the United States of America, 113 (37), 10400-5 PMID: 27573828