Dataset Information

Fecal Microbiota Transplants Annually and Their Positive Clinical Impact.

ABSTRACT: Introduction: Although fecal microbiota transplantation (FMT) is a recommended, clinically efficacious, and cost-effective treatment for recurrent Clostridioides difficile infection (CDI), the scale of FMT use in the United States is unknown.

Methods: We developed a population-level CDI model.

Results: We estimated that 48,000 FMTs could be performed annually, preventing 32,000 CDI recurrences.

Discussion: Improving access to FMT could lead to tens of thousands fewer C. difficile episodes per year.

SUBMITTER: Mamoon L

PROVIDER: S-EPMC7594930 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Fecal Microbiota Transplants Annually and Their Positive Clinical Impact.

Mamoon Lamia L Olesen Scott W SW

Clinical and translational gastroenterology 20201101 11

<h4>Introduction</h4>Although fecal microbiota transplantation (FMT) is a recommended, clinically efficacious, and cost-effective treatment for recurrent Clostridioides difficile infection (CDI), the scale of FMT use in the United States is unknown.<h4>Methods</h4>We developed a population-level CDI model.<h4>Results</h4>We estimated that 48,000 FMTs could be performed annually, preventing 32,000 CDI recurrences.<h4>Discussion</h4>Improving access to FMT could lead to tens of thousands fewer C. ...[more]

PMID: 33259159

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Project description:BackgroundFecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases.MethodsTo overcome these challenges, we developed methods to broaden FVT's clinical application while maintaining efficacy and increasing safety. Specifically, we employed the following approaches: (1) chemostat-fermentation to reproduce the bacteriophage FVT donor component and remove eukaryotic viruses (FVT-ChP), (2) solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT), and (3) pyronin-Y treatment to inhibit RNA virus replication (FVT-PyT). We assessed the efficacy of these processed FVTs in a C. difficile infection mouse model and compared them with untreated FVT (FVT-UnT), FMT, and saline.ResultsFVT-SDT, FVT-UnT, and FVT-ChP reduced the incidence of mice reaching the humane endpoint (0/8, 2/7, and 3/8, respectively) compared to FMT, FVT-PyT, and saline (5/8, 7/8, and 5/7, respectively) and significantly reduced the load of colonizing C. difficile cells and associated toxin A/B levels. There was a potential elimination of C. difficile colonization, with seven out of eight mice treated with FVT-SDT testing negative with qPCR. In contrast, all other treatments exhibited the continued presence of C. difficile. Moreover, the results were supported by changes in the gut microbiome profiles, cecal cytokine levels, and histopathological findings. Assessment of viral engraftment following FMT/FVT treatment and host-phage correlations analysis suggested that transfer of phages likely were an important contributing factor associated with treatment efficacy.ConclusionsThis proof-of-concept study shows that specific modifications of FVT hold promise in addressing challenges related to donor variability and infection risks. Two strategies lead to treatments significantly limiting C. difficile colonization in mice, with solvent/detergent treatment and chemostat propagation of donor phages emerging as promising approaches. Video Abstract.

Dataset Information

Fecal Microbiota Transplants Annually and Their Positive Clinical Impact.

Publications

Fecal Microbiota Transplants Annually and Their Positive Clinical Impact.

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