Enteric virome may be altered in inflammatory bowel disease

Last Updated: 2015-01-28

By Will Boggs MD

NEW YORK (Reuters Health) - Patients with inflammatory bowel disease (IBD) manifest specific alterations in the enteric virome that are not explained by decreases in bacterial diversity, researchers say.

"We found that the disruptions in the intestinal ecology of IBD patients are much more extensive than the previously reported disruptions in the bacterial microbiome," Dr. Herbert W. Virgin IV, from Washington University School of Medicine, St. Louis, told Reuters Health by email. "The virome is abnormal as well. Indeed, our findings indicate that changes in the virome, mostly in bacteriophages, and changes in intestinal bacteria may be interrelated. This opens up a new arena for possible treatments for these diseases."

Emerging data implicate the viral component of the microbiome (that is, the virome) in various aspects of human physiology, but whether the enteric virome plays a role in IBD has not been studied in detail.

Dr. Virgin's team characterized the normal and IBD human enteric virome by sequencing the DNA of virus-like particle preparations from fecal samples obtained from ulcerative colitis (UC) and Crohn disease (CD) patients and controls. They used two ecological metrics: richness (the number of taxa counted per sample) and diversity (a combination of richness and the relative abundance (or evenness) of the taxa present).

As expected, they observed decreases in bacterial richness and diversity in both UC and CD samples, compared to household controls, according to the January 22 online report in Cell.

Caudovirales order and Microviridae family were the most abundant viral taxa across all samples, but there was an increase in the richness of bacteriophages, particularly in members of Caudovirales, in IBD samples. There were, however, no increases in Microviridae richness or diversity.

The expansion of Caudovirales bacteriophages in IBD was inversely correlated to the reduction in bacterial richness and diversity, suggesting that bacteriophage expansion was not simply the result of increases in their bacterial hosts.

Moreover, there were striking differences in richness and the types of bacteriophage taxa between CD and UC samples, with each disease type harboring unique bacteriophages.

As for eukaryotic viruses, anellovirus sequences were more prevalent in IBD samples compared to healthy controls, but these sequences were not detected in all patients and did not correlate with disease activity or drug treatment.

"A main point that we hoped to make in the study is that we all need to think more broadly about all types of organisms in the intestine as possible contributors to ulcerative colitis and Crohn's disease," Dr. Virgin said. "We should not focus on bacteria alone, or viruses alone, and should be open to the involvement of other types of organisms as well."

"We are pondering how we might alter the virome to change the bacterial microbiome and vice versa," he said. "We are very interested in defining how this might be done through further research in both humans and animal models that we now seek to develop."

"We are far away from 'virome therapeutics' and there are many challenges, some perhaps related to the virome, for the use of fecal transplantation and bacterial probiotics," Dr. Virgin concluded. "I hope that physicians will be skeptical of unsubstantiated claims regarding the microbiome and will encourage their patients to become involved in ongoing research and clinical trials so that we can, in partnership, get to the bottom of these diseases. We are in an era of unprecedented opportunity for understanding these complex and difficult disorders."

Dr. Kenneth Cadwell, from New York University School of Medicine's Skirball Institute of Biomolecular Medicine, New York, recently reviewed the emerging understanding of the importance of the enteric virome. He told Reuters Health by email, "There is a lot of interest in manipulating bacteria, but let's not ignore the viruses. In fact, it is possible that difference in the virome between individuals has a bigger role in explaining disease than the difference in the bacterial microbiome."

"At this point, the virome holds a lot of promise, but it's too early to consider manipulating it for therapeutic purposes," Dr. Cadwell said. "But this paper is an excellent start, and they provide compelling evidence that the virome has prognostic or diagnostic value."

"The short-term implication is that bacteriophages are excellent biomarkers, perhaps even better than the bacterial members of the microbiome," Dr. Cadwell said. "The long-term implication is that understanding the role of the virome (collection of viruses) may be key to designing new and creative strategies to treat IBD."

SOURCE: http://bit.ly/1EAG8qb

Cell 2015.