Evidence map›Paper›PMID 38951925›Full record

ArticleMicrobiome2024

Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments.

Torben Sølbeck Rasmussen, Xiaotian Mao, Sarah Forster, Sabina Birgitte Larsen, Alexandra Von Münchow, Kaare Dyekær Tranæs, Anders Brunse, Frej Larsen, Josue Leonardo Castro Mejia, Signe Adamberg and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Microbiome, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  7. Article
  8. Article
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  10. Gut virome dynamics: from commensal to critical player in health and disease.Nature reviews. Gastroenterology & hepatology · 2026
    Review
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  15. Mucofilm: a nexus for phage-microbiome interactions in gut ecology.Applied and environmental microbiology · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Torben Sølbeck RasmussenSection of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Rolighedsvej 26 4, 1958, Frederiksberg, Denmark. torben@food.ku.dk.
Xiaotian MaoSection of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Rolighedsvej 26 4, 1958, Frederiksberg, Denmark.
Sarah ForsterSection of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Rolighedsvej 26 4, 1958, Frederiksberg, Denmark.
Sabina Birgitte LarsenSection of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Rolighedsvej 26 4, 1958, Frederiksberg, Denmark.
Alexandra Von MünchowSection of Experimental Animal Models, Department, of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9 1, 1871, Frederiksberg, Denmark.
Kaare Dyekær TranæsSection of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Rolighedsvej 26 4, 1958, Frederiksberg, Denmark.
Anders BrunseSection of Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Dyrlægevej 68, 1870, Frederiksberg, Denmark.
Frej LarsenSection of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Rolighedsvej 26 4, 1958, Frederiksberg, Denmark.
Josue Leonardo Castro MejiaSection of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Rolighedsvej 26 4, 1958, Frederiksberg, Denmark.
Signe AdambergDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, 12618, Tallinn, Estonia.
Axel Kornerup HansenSection of Experimental Animal Models, Department, of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9 1, 1871, Frederiksberg, Denmark.
Kaarel AdambergDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, 12618, Tallinn, Estonia.
Camilla Hartmann Friis HansenSection of Experimental Animal Models, Department, of Veterinary and Animal Sciences, University of Copenhagen, Ridebanevej 9 1, 1871, Frederiksberg, Denmark.
Dennis Sandris NielsenSection of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Rolighedsvej 26 4, 1958, Frederiksberg, Denmark. dn@food.ku.dk.

Funding

Novo Nordisk Fonden NNF-20OC0063874The Lundbeck Foundation R324-2019-1880
6 · The paper itself

Abstract

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.

Indexed as

BacteriophagesClostridioides difficileClostridium InfectionsFecal Microbiota TransplantationFecesGastrointestinal MicrobiomeAnimalsDisease Models, AnimalFemaleHumansMiceMice, Inbred C57BL

Identifiers

PMID38951925
PMCPMC11218093

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.