Opinion
Special Issue: Infection Biology in the Age of the Microbiome
Improving Risk–Benefit in Faecal Transplantation through Microbiome Screening

https://doi.org/10.1016/j.tim.2019.12.009Get rights and content

Highlights

  • FMT has demonstrated clinical efficacy for a growing number of conditions.

  • High rates of systemic infection in transplant recipients, and recent cases of sepsis caused by antibiotic-resistant pathogens transmitted through FMT, highlight the need to improve FMT safety.

  • Commensal gut microbes can substantially reduce sepsis risk through interactions with both pathogens and the host.

  • In addition to screening for pathogens, assessment of donor material should consider the composition and structure of the wider faecal microbiota.

  • Measures to protect commensal microbes during transplant preparation, and to deplete pathogen populations, could substantially improve the safety of FMT.

Faecal microbiota transplantation (FMT) has been shown to be effective in the treatment of a growing number of conditions, and its clinical use continues to rise. However, recent cases of antibiotic-resistant pathogen transmission through FMT, resulting in at least one case of fatal sepsis, highlight the need to reevaluate current donor screening practices. Commensal gut microbes profoundly influence infection risk but are not routinely assessed in donor stool. Extending the assessment of donor material beyond pathogen populations to include the composition and structure of the wider faecal microbiota has the potential to reduce infectious complications in FMT recipients.

Section snippets

The Clinical Potential of FMT

FMT has emerged as a transformative treatment for recurrent Clostridioides difficile infection (CDI) [1], providing outcomes that are substantially better that those associated with standard antibiotic therapy [2,3]. FMT involves the instillation of a preparation of donor stool into the intestinal tract of a patient, and has also shown promise in the treatment of noninfectious inflammatory bowel disorders and nonenteric conditions, particularly those relating to metabolic disease and

Safety Concerns

The increasingly widespread and often poorly regulated use of FMT has raised concerns about potential infection risks. Introducing a microbiologically complex material into a recipient is inherently hazardous, and the FDA recently reiterated its warning to patients that the procedure should be used only as a last resort [5]. A recent review of FMT safety found that serious adverse events occur in 2–6% of patients, depending on the route of administration [6]. The incidence of severe infections

The Influence of the Gut Microbiota on Infection

There are multiple complementary mechanisms by which commensal microbiota are able to prevent pathogen proliferation and infection. The majority of patients who receive FMT, such as those with C. difficile colitis, have substantial pre-existing depletion of commensal populations [13]. This disruption of the normal intestinal microbiota increases susceptibility to pathogen colonisation and is likely to explain the increased risk of subsequent sepsis in this population [14]. The relative ability

Approaches for Selecting or Improving Donor Microbiota Composition

Reduced faecal bacterial diversity is also associated with an increased risk of pathogen colonisation and systemic infection [17], suggesting this factor should be considered when assessing donor material. However, bacterial diversity is likely to be less important as an indicator of beneficial microbiota in its own right than as an indicator of the probability that the transplanted material contains specific microbial traits. In particular, the presence of beneficial keystone taxa can have a

FMT Processing to Preserve Microbiota Composition and Function

FMT material usually undergoes multiple processing steps, such as blending, filtering, and freezing, often performed under aerobic conditions. The processing methods used are highly variable and centre-specific.

The effects of processing on the viable microbiota composition of instilled material are not typically considered. However, certain processing steps, particularly blending in aerobic conditions, result in profound changes in the final viable microbiota composition that are not dissimilar

Modifying Donor Microbiota to Reduce Sepsis Risk

Stringent screening already makes the recruitment of suitable donors for FMT a major challenge. The exclusion of donors with an undesirable microbiota composition could result in a substantial further reduction in the donor pool. However, although inappropriate processing practices can modify the composition of the viable stool microbiota in a detrimental manner, modification of donated stool to improve its microbiological characteristics might allow material to be used from a wider donor

Overlap between Safety and Benefit

To date, interest in the microbiome traits of donor faeces has focused on improving treatment efficacy rather than safety [39]. However, there can be considerable overlap in achieving these separate goals. The same bacterial profiles that protect against infection and chronic disease (Box 4) also appear to be associated with clinical benefit following FMT. For example, donor-specific differences in clinical outcomes, also referred to as the super-donor effect, have been observed in the context

Can FMT Be Used to Prevent Pathogen Colonisation and Infection?

We began by discussing the transmission of drug-resistant bacterial pathogens through FMT. We will conclude by looking at the evidence that FMT can be used to achieve the opposite outcome: clearance of intestinal colonisation of drug-resistant pathogens, and reduced infection. First, FMT is capable of rapidly clearing colonisation by both VRE and carbapenem-resistant bacteria in murine models [47]. Several case studies have also temporally associated pathogen clearance with FMT [48,49]. In C.

Concluding Remarks

Efforts to improve the safety of FMT are essential but should not inadvertently undermine access to life-saving FMT for the treatment of CDI or discourage the investigation of FMT in clinical trials that could deliver important new therapeutic options for a range of diseases. Although current screening processes have an excellent track record of safety, much is still not known about how donor microbiota influence infection risk or which microbiome parameters should be used to screen donors (see

Glossary

Allogeneic stem-cell transplantation
transplantation from another person of cells with the ability to regenerate multiple types of new cells. This procedure is commonly used as part of the treatment of leukaemia and other blood cancers.
Bacterial diversity
the number, distribution, phylogenetic relatedness, and functional characteristics of the bacterial taxa associated with a given niche.
Bacteriocins
proteinaceous compounds produced by one type of bacteria that inhibit or kill other bacteria.

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