Fecal transplants are increasingly being used for refractory Clostridium difficile and other gastrointestinal disorders. While fecal donors are screened for various infectious diseases, it is unclear whether viruses can in fact be transmitted during fecal transplants. Now a new study shows that communities of viruses can be transferred during fecal transplants, but that the viruses that are transmitted are harmless to humans. The study was published this week in mBio, an online open-access journal of the American Society for Microbiology.
Fecal transplants are widely used for treating refractory Clostridium difficile infection, offering more than a 90% cure rate. “If you are taking antibiotics, particularly if you are elderly or hospitalized, you can disrupt your gut community and be colonized by a particularly nasty customer, C. difficile, and that can lead to severe GI problems. It can be fatal in the elderly,” said principal investigator of the new study Frederic Bushman, PhD, chair of the Department of Microbiology, Perelman School of Medicine, University of Pennsylvania. Fecal transplants are also being tried for other gastrointestinal ailments such as irritable bowel syndrome and ulcerative colitis.
During a fecal transplant, stool collected from a donor who has a healthy gastrointestinal tract is mixed with a solution (often saline), and then placed by colonoscopy, endoscopy, sigmoidsocopy, or enema into a patient with a gastrointestinal ailment. This transfers potentially “good” bacteria into a patient. Similar to blood donations, the donating candidate is tested for high-risk viruses such as HIV.
“Fecal transplants are widely used in medicine now and they work, but you might ask what viruses are moved along with the desirable bacteria?” said Dr. Bushman. “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.”
In the new study, the researchers analyzed the fecal transplants from a single, healthy donor to three children with chronic ulcerative colitis. The children received intensive treatment, a course of 22 to 30 transplants. The researchers purified viral particles from the poop of the donor and the recipients and conducted deep genomic sequencing to determine whether any viruses were transferred.
“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,” said Dr. Bushman. “We saw mostly temperate bacteriophages.”
A temperate virus does not always cause immediate lysis following entry to a host, but can adopt a latent state, replicating its genome along with the host’s genome after integration. These latent viruses can induce during times of stress, burst the cell, and liberate new viral particles into the environment. Some temperate bacteriophages can be of medical concern, such as ones that carry toxin genes or contribute to antibiotic resistance, but they are much less of a concern than animal cell viruses.
Temperate phages appeared to be transferred preferentially during fecal transplants. “We speculate that the temperate replication style exists, in part, to promote virus dispersal, to allow viruses to reach new environments where they can flourish,” said Dr. Bushman.
Future studies are planned to shed light on how viruses and populations of viruses move in and out of humans in similar scenarios, such as organ transplants. Dr. Bushman pointed out that before deep genome sequencing was available, this research would not have been possible.