© 2015 Peter Free
Citation — to study
Jason M. Norman, Scott A. Handley, Megan T. Baldridge, Lindsay Droit, Catherine Y. Liu, Brian C. Keller, Amal Kambal, Cynthia L. Monaco, Guoyan Zhao, Phillip Fleshner, Thaddeus S. Stappenbeck, Dermot P.B. McGovern, Ali Keshavarzian, Ece A. Mutlu, Jenny Sauk, Dirk Gevers, Ramnik J. Xavier, David Wang, Miles Parkes, and Herbert W. Virgin, Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease, Cell, DOI: 10.1016/j.cell.2015.01.002 (online now, 22 January 2015))
Citation — to press release
Michael C. Purdy, Viruses may play unexpected role in inflammatory bowel diseases, Washington University in St. Louis (22 January 2015)
From the arguably poorly communicated abstract
The finding in this study may boil down to the fact that the volume and diversity of “free” Caudovirales bacteriophages — meaning those outside the bacteria they usually inhabit — may be increased in patients with inflammatory bowel conditions (like Chron’s and ulcerative colitis), as compared to controls.
Alternatively, the finding may be that the volume of loose Caudovirales bacteriophages and noticeable volumes of other viruses are both increased:
Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases.
We show that the enteric virome is abnormal in CD and UC patients.
In-depth analysis of preparations enriched for free virions in the intestine revealed that CD and UC were associated with a significant expansion of Caudovirales bacteriophages.
The viromes of CD and UC patients were disease and cohort specific. Importantly, it did not appear that expansion and diversification of the enteric virome was secondary to changes in bacterial populations.
These data support a model in which changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis.
We conclude that the virome is a candidate for contributing to, or being a biomarker for, human inflammatory bowel disease and speculate that the enteric virome may play a role in other diseases.
© 2015 Jason M. Norman, Scott A. Handley, Megan T. Baldridge, Lindsay Droit, Catherine Y. Liu, Brian C. Keller, Amal Kambal, Cynthia L. Monaco, Guoyan Zhao, Phillip Fleshner, Thaddeus S. Stappenbeck, Dermot P.B. McGovern, Ali Keshavarzian, Ece A. Mutlu, Jenny Sauk, Dirk Gevers, Ramnik J. Xavier, David Wang, Miles Parkes, and Herbert W. Virgin, Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease, Cell, DOI: 10.1016/j.cell.2015.01.002 (online now, 22 January 2015) (paragraph split, underline added)
Regarding the abstract’s opaque language
Notice that the abstract and its title loosely conflate the more general terms, “viral” load and “virome” with the more specific term, Caudovirales bacteriophages. Thus, we cannot tell whether the team found:
(a) both an increase in viruses (of apparently many kinds) and a proportionately noticeable increase in loose Caudovirales bacteriophages
(b) mainly an increase in loose Caudovirales bacteriophages.
Second, the abstract adds the mildly counterintuitive statement that bacterial populations remained the same, despite the fact that a loose Caudovirales bacteriophage population(s) presumably came from dead or dying bacteria.
Given that it seems unlikely that different species of bacteria would all be equally affected by whatever causes them to lose their Caudovirales bacteriophage DNA bits, it does not make obvious sense, when the authors simultaneously suspect that “the virome may contribute to intestinal inflammation and bacterial dysbiosis.”
Dysbiosis is an unnecessarily imprecise and fancy word for “microbial imbalance”.
Which in this context we can assume to mean that the research team suspects that the heightened viral load has something to do with the reduced diversity and population(s) of intestinal bacteria.
Maybe and equally, maybe not. One could just easily assume that:
(a) if the Caudovirales bacteriophage population comes from dying bacteria,
(ii) then it is whatever is killing the bacteria that causes inflammatory disease
(iii) not the associated change in loose bacteriophage volume/diversity that is the culprit.
One could hypothesize the same thing for many or all of the other viruses, as well.
As is it turns out, the abstract’s arguably unclear wording merely reflects the confusion that almost always attends a preliminary investigation
According to Michael Purdy’s much more informative press release, the research team has no idea which viruses it is dealing with or how they got there:
The Centers for Disease Control and Prevention estimates that inflammatory bowel diseases affect about 1 million people in the United States.
Crohn’s disease and ulcerative colitis are thought to involve misdirected immune attacks on gut tissue and can lead to weight loss, bleeding in the gut and rectum, and loss of appetite. Surgery to remove part of the bowel is often necessary to treat Crohn’s disease.
Virgin and his colleagues studied three groups of patients with Crohn’s disease or ulcerative colitis living in Chicago, Boston and the United Kingdom.
In each group, they compared viral DNA purified from the feces of participants with viral DNA from the feces of healthy people living in the same areas and, in some cases, the same homes.
The findings suggest that scientists should be studying the virome as closely as the microbiome, said senior author Herbert W. Virgin IV, MD, PhD.
“This is the tip of the iceberg,” he said.
“A significant portion of the viral DNA we identified in these patients is unfamiliar to us — it comes from newly identified viruses we don’t know much about.
“We have a great deal of groundwork to do, including sequencing the genetic material of these viruses and learning how they interact with the gut and gut bacteria, before we can determine if changes in the virome cause these conditions or result from them.”
“Much of the increased viral diversity in participants with inflammatory bowel diseases was in the form of bacteriophages, which are viruses that infect bacteria and can incorporate themselves into the bacteria’s genetic material,” said Virgin . . . head of the Department of Pathology and Immunology.
Changes in the gut that eliminate bacteria in inflammatory bowel diseases may unleash bacteriophages in the dying bacteria, Virgin speculated.
Or the introduction of a new bacteriophage to the gut, perhaps through the foods in a person’s diet, may trigger a reaction in the digestive system or the microbiome that causes the disorders, he said. It’s also possible that a combination of these mechanisms may contribute.
© 2015 Michael C. Purdy, Viruses may play unexpected role in inflammatory bowel diseases, Washington University in St. Louis (22 January 2015) (extracts, italics added)
The moral? — Interesting, probably valuable, but too early to say more than that
Excellent work, but somewhat clumsily reported in the abstract. Kudos to Michael Purdy for clearing the confusion with his informative press release.