title: Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation.
abstract: Fecal microbiota transplantation (FMT) is a highly effective treatment for refractoryClostridium difficileinfections. However, concerns persist about unwanted cotransfer of pathogenic microbes such as viruses. Here we studed FMT from a single healthy human donor to three pediatric ulcerative colitis patients, each of whom received a course of 22 to 30 FMT treatments. Viral particles were purified from donor and recipient stool samples and sequenced; the reads were then assembled into contigs corresponding to viral genomes or partial genomes. Transfer of selected viruses was confirmed by quantitative PCR. Viral contigs present in the donor could be readily detected in recipients, with up to 32 different donor viral contigs appearing in a recipient sample. Reassuringly, none of these were viruses are known to replicate on human cells. Instead, viral contigs either scored as bacteriophage or could not be attributed taxonomically, suggestive of unstudied phage. The two most frequently transferred gene types were associated with temperate-phage replication. In addition, members ofSiphoviridae, the group of typically temperate phages that includes phage lambda, were found to be transferred with significantly greater efficiency than other groups. On the basis of these findings, we propose that the temperate-phage replication style may promote efficient phage transfer between human individuals. In summary, we documented transfer of multiple viral lineages between human individuals through FMT, but in this case series, none were from viral groups known to infect human cells.
  
  
  OBJECTIVE
  Transfer of whole communities of viruses between humans has rarely been studied but is of likely medical importance. Here we studied fecal microbiota transplantation (FMT), a highly successful treatment for relapsingClostridium difficileinfection and, potentially, other gastrointestinal (GI) diseases. We investigated the transfer of viral communities during FMT and documented transfer of multiple viral lineages between humans. None of these were viruses that replicated on animal cells or that are known to be pathogenic. We found that temperate bacteriophage, which form stable associations with their hosts, were significantly more likely to be transferred during FMT. This supports a model in which the viral temperate replication style may have evolved in part to support efficient viral transmission between environments.
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Christel
authors.initials: C
authors.lastname: Chehoud
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA Department of Chemistry, Saint Petersburg State University, Saint Petersburg, Russia.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Dryga
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Young
authors.initials: Y
authors.lastname: Hwang
authors.affiliation: Section of Pediatric Gastroenterology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, USDA/ARS Children's Nutrition Research Center, Houston, Texas, USA.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Nagy-Szakal
authors.affiliation: Texas Children's Microbiome Center, Department of Pathology, Texas Children's Hospital, Houston, Texas, USA Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Hollister
authors.affiliation: Texas Children's Microbiome Center, Department of Pathology, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Ruth Ann
authors.initials: RA
authors.lastname: Luna
authors.affiliation: Texas Children's Microbiome Center, Department of Pathology, Texas Children's Hospital, Houston, Texas, USA Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: James
authors.initials: J
authors.lastname: Versalovic
authors.affiliation: Section of Pediatric Gastroenterology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, USDA/ARS Children's Nutrition Research Center, Houston, Texas, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Kellermayer
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA bushman@upenn.edu.
authors.forename: Frederic D
authors.initials: FD
authors.lastname: Bushman
mesh_terms: D044822:Biodiversity; D003093:Colitis, Ulcerative / Q000628:therapy*; D000069467:Fecal Microbiota Transplantation / Q000009:adverse effects*; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014780:Viruses / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*