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Researchers See IBD-related Shifts in Individuals' Gut Viromes

NEW YORK (GenomeWeb) – Individuals with inflammatory bowel disease appear prone to changes in the collection of viruses present in their guts, according to a study published online today in Cell.

Researchers from Washington University and other centers in the US and UK used metagenomic sequencing to compare gut virus richness and diversity patterns in individuals with or without IBD from the same households. Their results revealed a rise in gut virome diversity in individuals with IBD, particularly when it came to the representation of bacteria-infecting viruses from the Caudovirales order.

"We know that mutations in human genes affect the risk of inflammatory bowel diseases," senior author Herbert Virgin, head of pathology and immunology at Washington University, said in a statement, "and scientists also are exploring how bacterial genes may influence risk."

"Our results show that the virome's potential effects on the gut also need to be a part of these investigations," he added.

Bacteria have been credited with helping to establish immune features of the intestinal mucosa, while curtailing excessive inflammation, the study's authors explained. And the presence of IBD has been linked to unusual gut microbiome features such as lower-than-usual diversity overall, a dip in representation by Bacteroidetes and Firmicutes bacteria, and a rise in levels of bugs that are usually relatively scarce.

Moreover, they noted that "household contacts without IBD can also exhibit signs of bacterial dysbiosis. These individuals have increased intestinal permeability compared to healthy community controls, suggesting that the bacterial microbiome is heavily influenced by the household environment."

Similarly, past research hints that the collection of viruses an individual carries can impact his or her physiological features, though less is known about the ways that viruses are swapped back and forth between members of the same household.

To assess the viral component of the gut microbiome in IBD-affected and -unaffected individuals from the same household, the researchers started by doing Roche 454 metagenomic sequencing on DNA from stool samples of 18 individuals with Crohn's disease, 42 individuals with ulcerative colitis, and a dozen unaffected individuals from the same households.

Their results suggest that gut viromes from individuals with ulcerative colitis are more likely to contain bacteriophages — bacteria-infecting viruses — from the Caudovirales order of double-stranded DNA viruses, but fewer Microviridae family bacteriophages, which are composed of single-stranded DNA.

Likewise, individuals with Crohn's disease showed a rise in representation by Caudovirales bacteriophages, though their Microviridae levels were more similar to those seen in healthy controls from the same household.

When investigators used the Illumina MiSeq instrument to specifically sequence virus-like particles enriched from dozens of stool samples for affected and unaffected individuals from 17 households, they found that the IBD samples contained somewhat more diverse reads and viral representation, along with higher Caudovirales bacteriophage levels.

Those gut virome shifts seemed to coincide with a decline in bacterial diversity and richness in those with Crohn's disease or ulcerative colitis, which the team detected with the help of Illumina 16S ribosomal RNA sequencing on stool samples.

Comparable virome patterns turned up when the team tested dozens more individuals with or without IBD from two cohorts in the US and the UK, though the precise gut virome shifts detected seemed to vary depending on the condition considered and the cohort at hand.

From their findings so far, the study's authors speculated that the gut virome may eventually serve as a source of information when diagnosing or even treating IBD, though they emphasized that more work is needed to map out the viral and bacterial interactions that might impact the conditions.

"We have a great deal of groundwork to do," Virgin said, "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."