Faecal microbiota transplantation for
            <i>Clostridium difficile</i>
            infection: a multicentre study of non‐responders

Razik, Roshan; Osman, Majdi; Lieberman, Alexandra; Allegretti, Jessica R.; Kassam, Zain

doi:10.5694/mja16.01452

Cited by 5 publications

(10 citation statements)

References 5 publications

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“…A machine-learning method to predict the gut microbiota of the post-FMT patients was also developed, using both clinical and metagenomics data of the donor and the pre-FMT patient 79 . Several multicenter studies 58,90 focused on the identification of clinical risk factors that are associated with FMT failure (without using microbiome data).…”

Section: Discussionmentioning

confidence: 99%

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An ecological framework to understand the efficacy of fecal microbiota transplantation

et al. 2020

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Human gut microbiota plays critical roles in physiology and disease. Our understanding of ecological principles that govern the dynamics and resilience of this highly complex ecosystem remains rudimentary. This knowledge gap becomes more problematic as new approaches to modifying this ecosystem, such as fecal microbiota transplantation (FMT), are being developed as therapeutic interventions. Here we present an ecological framework to understand the efficacy of FMT in treating conditions associated with a disrupted gut microbiota, using the recurrent Clostridioides difficile infection as a prototype disease. This framework predicts several key factors that determine the efficacy of FMT. Moreover, it offers an efficient algorithm for the rational design of personalized probiotic cocktails to decolonize pathogens. We analyze data from both preclinical mouse experiments and a clinical trial of FMT to validate our theoretical framework. The presented results significantly improve our understanding of the ecological principles of FMT and have a positive translational impact on the rational design of general microbiota-based therapeutics.

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Section: Discussionmentioning

confidence: 99%

“…We have only recently started to understand the molecular mechanisms of FMT in treating rCDI [50][51][52][53][54][55][56] . We still do not quite understand why~20% of rCDI patients relapse after FMT 27,57,58 . Very little is known about the long-term effects of FMT from the ecological perspective 54 .…”

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confidence: 99%

An ecological framework to understand the efficacy of fecal microbiota transplantation

et al. 2020

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“…Since a 1-day PEG treatment resulted in a more mild perturbation of the microbiota, we decided to use the 1-day treatment to examine the hypothesis that PEG helps to flush C. difficile spores from the intestine. This hypothesis is proposed in the discussion section of FMT studies where bowel prep is part of the preparation undergone by patients receiving FMTs via colonoscopy (20)(21)(22)(23). To examine the impact of PEG treatment on C. difficile clearance, we treated 4 groups of mice with clindamycin and then challenged all mice with C. difficile before administering the following treatments: no additional treatment, 1-day PEG immediately after challenge, and 1-day PEG treatment 3 days after challenge followed by either administration of an FMT or PBS solution by oral gavage (Fig.…”

Section: Difficile Colonization Resistancementioning

confidence: 99%

“…For FMTs that are delivered via colonoscopy, patients typically undergo bowel preparation by taking an osmotic laxative prior to the procedure. Many of the FMT studies to date rationalize the use of laxatives prior to the FMT (20)(21)(22) based on a 1996 case study with 2 pediatric patients where the authors suggested in the discussion that the laxative may help flush C. difficile spores and toxins from the intestine (23).…”

Section: Introductionmentioning

confidence: 99%

An osmotic laxative renders mice susceptible to prolonged Clostridioides difficile colonization and hinders clearance

Tomkovich

Taylor

King

et al. 2021

Preprint

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Antibiotics are a major risk factor for Clostridioides difficile infections (CDIs) because of their impact on the microbiota. However, non-antibiotic medications such as the ubiquitous osmotic laxative polyethylene glycol (PEG) 3350 also alter the microbiota. Clinicians also hypothesize that PEG helps clear C. difficile. But whether PEG impacts CDI susceptibility and clearance is unclear. To examine how PEG impacts susceptibility, we treated C57Bl/6 mice with 5-day and 1-day doses of 15% PEG in the drinking water and then challenged the mice with C. difficile 630. We used clindamycin-treated mice as a control because they consistently clear C. difficile within 10 days post-challenge. PEG treatment alone was sufficient to render mice susceptible and 5-day PEG-treated mice remained colonized for up to 30 days post-challenge. In contrast, 1-day PEG treated mice were transiently colonized, clearing C. difficile within 7 days post-challenge. To examine how PEG treatment impacts clearance, we administered a 1-day PEG treatment to clindamycin-treated, C. difficile-challenged mice. Administering PEG to mice after C. difficile challenge prolonged colonization up to 30 days post-challenge. When we trained a random forest model with community data from 5 days post-challenge, we were able to predict which mice would exhibit prolonged colonization (AUROC = 0.90). Examining the dynamics of these bacterial populations during the post-challenge period revealed patterns in the relative abundances of Bacteroides, Enterobacteriaceae, Porphyromonadaceae, Lachnospiraceae, and Akkermansia that were associated with prolonged C. difficile colonization in PEG-treated mice. Thus, the osmotic laxative, PEG, rendered mice susceptible to C. difficile colonization and hindered clearance.

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“…Practice has already evolved from using stool provided by a recipient‐selected donor to employing cryopreserved stool donated by screened healthy donors. Success with thawed material and experience with stool banking has been positive, as documented by Razik and colleagues in this issue of the Journal 11 . The time is not far off, however, when whole stool, whether fresh or preserved, will no longer be used; instead, a designer infusion or capsule of selected microorganisms, either alone or combined with a microbiotic metabolic product, will be given to restore a balanced microbiota.…”

mentioning

confidence: 98%

Faecal microbiota transplantation: past, present and future

Brandt

2017

Medical Journal of Australia

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Faecal microbiota transplantation for Clostridium difficile infection: a multicentre study of non‐responders

Cited by 5 publications

References 5 publications

An ecological framework to understand the efficacy of fecal microbiota transplantation

An ecological framework to understand the efficacy of fecal microbiota transplantation

An osmotic laxative renders mice susceptible to prolonged Clostridioides difficile colonization and hinders clearance

Faecal microbiota transplantation: past, present and future

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