The future of faecal transplants

The introduction of faecal transplants has provided a new and welcome approach to treating difficult bacterial infections. However, following a patient death, there are questions over their future use. How can the risks surrounding transplants be removed to reap the benefits of this promising therapeutic treatment?

In this review, published in Nature Reviews Microbiology, Hudson Institute microbiome experts Dr Edward Giles, Gemma D’Adamo and Dr Sam Forster say there is an urgent need for the standardised regulation of faecal microbiota transplant (FMT) treatments.

In a burgeoning FMT industry where treatments are being used in medicine, as well as a large number of treatments moving into clinical trials, the team outline what they see as the next steps to ensure safer microbiota-based medicines.

Success of FMT to-date

FMTs offer an alternative treatment to antibiotics for bacterial infections, which is increasingly becoming an important therapeutic option as many bacteria develop drug-resistant strains.

The potential role of microbiota-based medicines is immense and could help cure a wide range of conditions, from diabetes to obesity.

FMT involves transplanting healthy stool bacteria to a patient. The process balances gut bacteria through the reintroduction of healthy bacteria. The treatment is referred to as ‘non-specific’, meaning that the entire microbiome of the donor’s stool is transferred, not particular bacteria types.

The transplant can be administered in a number of ways including colonoscopy, enema, or a capsule containing freeze-dried material.

FMT has been highly successful in treating the debilitating intestinal infection that is caused by the Clostridioides difficile bacteria. The infection causes diarrhoea, fever, stomach pain and nausea. One of the worst traits of the bacteria is its ability to reinfect patients, with one in five patients having a reoccurrence.

C. diff infections are a prime target for treatment by faecal transplant because the bacteria are hard to kill, due to the fact they can produce spores that can tolerate extreme conditions. In fact, some antibiotic therapies can make the infection worse by disrupting the normal balance of the gut bacteria, which allows C. diff to opportunistically dominate.

To compound the difficulty of treating C. diff, globally strains of the bacteria are emerging that are antibiotic resistant.

Dr Forster said, “Randomised controlled trials of FMT for treating of C. diff infections have reported more than 90 per cent efficacy, largely irrespective of preparation and administration strategy.

“C. diff is a great example of a difficult to treat infection that responds very effectively to FMT. It illustrates the kind of application and potential FTM therapies can have.”

Risks

Dr Forster said, “Despite the non-specific nature of the treatment, FMT has shown a remarkably low rate of negative patient responses.

“However, the transfer of live microorganisms from healthy donors to sick patients has risks.

“Recently in the USA, an FMT containing drug-resistant bacteria was transferred to a patient, who subsequently died.

“When this is viewed in alongside three previous reports of FMT fatalities, it’s clear there are some serious issues that need to be addressed.

“The risk of infection, although small, depends on the FMT sample. Infection risk is possibly higher in patients with disturbed microbiota, such as those who have recently undergone antibiotic treatment.”

Next steps | microbiological screening

“While further work needs to be done, it is great to see the Australian Therapeutic Goods Administration and the Minister for Health’s recent announcement of guidelines that regulate the use of FMT and ensure patient safety in Australia,” Dr Forster said.

Dr Giles said, “FMT definitely should be available as a treatment option, it is often a lifesaving procedure. However, we need industry-wide regulatory standards.

“In the recent case of the patient who died from FMT, the donor stool had not been tested, and subsequent testing showed the transplant had administered drug-resistant bacteria.

“The use of standard microbiological screening should prevent transferring known disease-causing microorganisms and antimicrobial resistant bacteria to sick patients.

“Being able to safely deliver FMT to patients will require standardised, highly specialised laboratories for stool preparation and thorough screening of donor material.”

Targeted treatments

Dr Giles said, “Due to the complexity and variability in donor stools, coupled with our limited understanding of the forces that shape the microbiota, FMT will always present a risk for some patients.

“Ultimately we see non-specific FMT as a therapeutic bridge to a more targeted treatment. We see a future where instead of transferring the whole microbiome of a donor, targeted bacteriotherapy where one type of good bacteria, or a handful of good bacteria, are administered to patients to restore their gut health.

“The future of treatment could be a multi-faceted approach, taking into account our knowledge of healthy microbiota and how diet impacts our microbiome. This could see patients using a combination of antibiotics, followed by targeted bacteriotherapy and changes to diet to cure their condition.

“This future treatment is not too far on the horizon, with work already underway to create tailor-made treatments with specific beneficial bacteria.”