Dataset Information

Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation.

ABSTRACT:

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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.

Importance

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.

SUBMITTER: Chehoud C

PROVIDER: S-EPMC4817255 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation.

Chehoud Christel C Dryga Anatoly A Hwang Young Y Nagy-Szakal Dorottya D Hollister Emily B EB Luna Ruth Ann RA Versalovic James J Kellermayer Richard R Bushman Frederic D FD

mBio 20160329 2

<h4>Unlabelled</h4>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 assembl ...[more]

PMID: 27025251

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Project description:BackgroundThere is growing evidence that fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection, but little guidance exists for implementation of FMT programs. The objective of this study is to describe the program characteristics and protocols of 9 planned or operating FMT programs in the Southern Ontario Fecal Microbiota Transplantation (SOFT) Movement, to help guide future FMT program implementation.MethodsA 59-item survey was administered electronically to clinical leads of the SOFT Movement on June 2, 2016. The survey evaluated 7 domains: FMT program characteristics, FMT recipients, donor screening/selection, transplant manufacturing, FMT administration, good manufacturing procedures/biosafety procedures and infection-control procedures. We used descriptive statistics to analyze quantitative data.ResultsAll 9 programs responded to the survey: 6 were active, 1 had FMT standard operating procedures developed but did not have clinical experience, and 2 were in the process of forming FMT programs. All 6 active programs performed FMT in adult patients with C. difficile infection. About 1300 FMT procedures were performed between 2003 and 2016. Five of the 6 operating programs administered the preparation via enema. Programs were driven primarily by physicians. All programs used universal FMT donors and followed Health Canada's screening guidelines, with considerable variability in screening frequency (every 3-6 mo) and modality. Locations for transplant preparation and manufacturing protocols varied across programs. Stool mass for FMT ranged from 20 g to 150 g, and transplant volume ranged from 25 mL to 300 mL.InterpretationThe experience of this high-volume regional FMT network highlights current challenges in FMT program development, including a high reliance on physicians and the costly nature of donor screening. Standardization and optimization through development of regional centres of excellence for FMT donor recruitment and administration should be explored.

Project description:Background: Several studies suggested an important role of the gut microbiota in the pathophysiology of neurological disorders, implying that alteration of the gut microbiota might serve as a treatment strategy. Fecal microbiota transplantation (FMT) is currently the most effective gut microbiota intervention and an accepted treatment for recurrent Clostridioides difficile infections. To evaluate indications of FMT for patients with neurological disorders, we summarized the available literature on FMT. In addition, we provide suggestions for future directions. Methods: In July 2019, five main databases were searched for studies and case descriptions on FMT in neurological disorders in humans or animal models. In addition, the ClinicalTrials.gov website was consulted for registered planned and ongoing trials. Results: Of 541 identified studies, 34 were included in the analysis. Clinical trials with FMT have been performed in patients with autism spectrum disorder and showed beneficial effects on neurological symptoms. For multiple sclerosis and Parkinson's disease, several animal studies suggested a positive effect of FMT, supported by some human case reports. For epilepsy, Tourette syndrome, and diabetic neuropathy some studies suggested a beneficial effect of FMT, but evidence was restricted to case reports and limited numbers of animal studies. For stroke, Alzheimer's disease and Guillain-Barré syndrome only studies with animal models were identified. These studies suggested a potential beneficial effect of healthy donor FMT. In contrast, one study with an animal model for stroke showed increased mortality after FMT. For Guillain-Barré only one study was identified. Whether positive findings from animal studies can be confirmed in the treatment of human diseases awaits to be seen. Several trials with FMT as treatment for the above mentioned neurological disorders are planned or ongoing, as well as for amyotrophic lateral sclerosis. Conclusions: Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.

Dataset Information

Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation.

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Publications

Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation.

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