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Metagenomic Sequencing Study IDs Viral Particles Transferred During Fecal Transplantation

NEW YORK (GenomeWeb) – A new mBio study is documenting the viruses that get passed along when individuals are treated using fecal transplants.

Researchers from the US and Russia used metagenomic sequencing and 16S ribosomal RNA sequencing to profile viruses and bacteria in stool samples from three children with ulcerative colitis who received fecal microbiota transplants from the same healthy adult donor.

For the most part, the viruses transferred from the donor to the recipients seemed to come from groups known for infecting bacteria themselves, known as temperate bacteriophages. Although some of the sequences picked up came from uncharacterized viruses, the team did not see examples of transferred viruses that were pathogenic or could replicate in human cells in their follow-up experiments.

"We could see bacterial viruses moving between humans and we were able to learn some things about transmission," senior author Frederic Bushman, microbiology chair at the University of Pennsylvania's school of medicine, said in a statement, "but we did not see any viruses that grow on animal cells that may be of concern for infecting and harming patients."

Such analyses are expected to help in teasing apart the full suite of risks, benefits, and consequences of fecal transplantation, which is increasingly being used to treat persistent or relapsing Clostridium difficile infections and other conditions.

To get a better sense of the viral communities that get passed between individuals during fecal transplantation, Bushman and his colleagues focused on three pediatric ulcerative colitis patients who received between 22 and 30 fecal transplants over the course of six weeks to three months from a healthy 37-year-old man.

Prior to fecal transplantation, each of the children received immunotherapy treatments. Though fecal transplant led to remission from ulcerative colitis symptoms in the weeks following the treatment, all of the children eventually relapsed and went back to immunotherapy in the long term.

After purifying viral particles from donor samples and recipient stool samples collected before, during, and after fecal transplantation, the researchers used Illumina MiSeq instruments to sequence viral material. For comparative purposes, they also sequenced viral particles in samples from several controls, including a healthy adult male and two children with Crohn's disease.

The team put the resulting sequence viral reads together to form complete or partial genomes, and compared them with available sequence databases. Viruses from the Microviridae family of phages turned up most frequently in the stool samples, the researchers reported. When they looked at potential viral transfer from the fecal transplant donor to the recipients, they saw dozens of donor-like viral contigs that showed up in the patients after fecal transplantation, including four virus-like particles transmitted to more than one recipient.

The team's subsequent quantitative PCR experiments supported the notion that these virus-like particles were transferred from the donor to recipients, with bacteria- or archaebacteria-infecting viruses from the Siphoviridae family apparently moving most often between individuals.

"Transmission of gut viruses between human hosts potentially involves persistence outside the gut, likely representing a transmission barrier," Bushman and co-authors wrote. "[W]e propose that the temperate-phage replication style may in part have evolved to maximize survival during transmission."

On the bacterial side, meanwhile, the researchers' 16S ribosomal RNA gene sequencing experiments revealed an over-representation of Bacteroides species in the healthy donor, but lower levels of Firmicutes, species. The pediatric ulcerative colitis patients also had high levels of Bacteroides bacteria, both before and during fecal transplantation.

The overall bacterial diversity increased in the recipients after fecal transplantation, while two of the children had a jump in representation by Firmicutes bacteria in their gut microbiomes after treatment.