Abstract
ABSTRACTFecal microbiota transplantation (FMT) is a highly effective treatment for refractory Clostridium difficile infections. 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 of Siphoviridae, 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.
Highlights
Fecal microbiota transplantation (FMT) is a highly effective treatment for refractory Clostridium difficile infections
Three pediatric ulcerative colitis (UC) patients receiving immunotherapy regimens were switched to receiving a course of 22 to 30 FMT treatments via colonoscopy or enema during a 6 to 12 week period (Fig. 1A) [15]
We report transfer of gut viral communities associated with FMT
Summary
Fecal microbiota transplantation (FMT) is a highly effective treatment for refractory Clostridium difficile infections. 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 None of these were viruses are known to replicate on human cells. 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. Sequencing total DNA from stool and aligning to database genomes generally misses most of the bacteriophage sequences present, necessitating specialized methods
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