In the Journals

Nonpathogenic viral communities transferred during FMT for refractory C. difficile infection

Viral communities can be transferred from donor to recipient during fecal microbiota transplantation for the treatment of refractory Clostridium difficile infection, but these viruses appeared to be nonpathogenic, according to recent research.

“Fecal transplants are widely used in medicine now and they work, but you might ask what viruses are moved along with the desirable bacteria,” Frederic Bushman, PhD, chair of the department of microbiology at Perelman School of Medicine, University of Pennsylvania, said in a press release. “The donors are screened very extensively for GI diseases and other infectious diseases, however you worry about the unknown unknowns, infectious agents that might be bad, but not screened for.”

Bushman and colleagues evaluated 18 stool samples obtained from a single FMT donor and three children with ulcerative colitis before, during and after the procedures. FMTs were administered by colonoscopy or enema during 22 to 30 treatments over 6 to 12 weeks. They purified and sequenced viral particles from both donor and recipient stool samples, analyzed the viral genomes, and then confirmed the transfer of selected viruses using quantitative polymerase chain reaction.

“We could see bacterial viruses moving between humans and we were able to learn some things about transmission, but we did not see any viruses that grow on animal cells that may be of concern for infecting and harming patients,” Bushman said. “We saw mostly temperate bacteriophages.”

They found as many as 32 viral contigs present in the donor stool appeared in recipient stool samples. Fortunately, none of them were known pathogens; they were either bacteriophages or not taxonomically identifiable. Siphoviridae were more efficiently transferred compared with other groups (P < .0001).

“On the basis of these observations, we propose that transfer of bacteriophage populations is a general characteristic of FMT,” the researchers concluded. “An alternative interpretation for our data could be that viruses were not transferred from donor to recipients but instead were present in recipients at levels that were initially below the level of detection. According to this view, viruses preexisting in the recipient would have grown out after FMT, resulting in the spurious appearance of transfer. We cannot completely rule out this possibility, but several aspects of phase biology in the human gut support our interpretation.” – by Adam Leitenberger

Disclosure: This study was funded by the PennCHOP Microbiome Program, Gutsy Kids Fund and NIH.

Viral communities can be transferred from donor to recipient during fecal microbiota transplantation for the treatment of refractory Clostridium difficile infection, but these viruses appeared to be nonpathogenic, according to recent research.

“Fecal transplants are widely used in medicine now and they work, but you might ask what viruses are moved along with the desirable bacteria,” Frederic Bushman, PhD, chair of the department of microbiology at Perelman School of Medicine, University of Pennsylvania, said in a press release. “The donors are screened very extensively for GI diseases and other infectious diseases, however you worry about the unknown unknowns, infectious agents that might be bad, but not screened for.”

Bushman and colleagues evaluated 18 stool samples obtained from a single FMT donor and three children with ulcerative colitis before, during and after the procedures. FMTs were administered by colonoscopy or enema during 22 to 30 treatments over 6 to 12 weeks. They purified and sequenced viral particles from both donor and recipient stool samples, analyzed the viral genomes, and then confirmed the transfer of selected viruses using quantitative polymerase chain reaction.

“We could see bacterial viruses moving between humans and we were able to learn some things about transmission, but we did not see any viruses that grow on animal cells that may be of concern for infecting and harming patients,” Bushman said. “We saw mostly temperate bacteriophages.”

They found as many as 32 viral contigs present in the donor stool appeared in recipient stool samples. Fortunately, none of them were known pathogens; they were either bacteriophages or not taxonomically identifiable. Siphoviridae were more efficiently transferred compared with other groups (P < .0001).

“On the basis of these observations, we propose that transfer of bacteriophage populations is a general characteristic of FMT,” the researchers concluded. “An alternative interpretation for our data could be that viruses were not transferred from donor to recipients but instead were present in recipients at levels that were initially below the level of detection. According to this view, viruses preexisting in the recipient would have grown out after FMT, resulting in the spurious appearance of transfer. We cannot completely rule out this possibility, but several aspects of phase biology in the human gut support our interpretation.” – by Adam Leitenberger

Disclosure: This study was funded by the PennCHOP Microbiome Program, Gutsy Kids Fund and NIH.