Could faecal transplants be an effective weapon in the fight back against antibiotic resistance? A research team at Guy’s and St Thomas’ NHS Foundation Trust intends to find out, once and for all.
By HELEN COMPSON
While faecal transplants have been used in medical settings since the 1940s to treat the stubborn infection that is Clostridium difficile, it wasn’t until the early noughties that the first clinical trials took place to establish whether the anecdotal evidence that spoke for their efficacy held water.
Good, randomised control evidence did indeed begin to emerge, indicating a patient in the grip of C.diff. – a potentially fatal infection characterised by inflammation of the colon and severe diarrhoea – could be rescued with an infusion of good bacteria donated by a healthy individual.
But an even more exciting possibility began to open up when it was realised that many of those same C.diff. patients also had antibiotic resistant bacteria in their gut too.
Dr Blair Merrick, Clinical Research Fellow and trial co-ordinator at Guy’s and St Thomas’s, said: “That in itself isn’t much of a surprise, because if someone has been given a lot of antibiotics, they are at greater risk of developing C.diff. in the first place – antibiotics kill bacteria good and bad, allowing bad bacteria to then become the dominant species.
“What was interesting though was the finding that where people had both C.diff. and antibiotic resistant organisms in their gut and were successfully treated for the former with faecal transplant, the latter seemed to disappear as well.”
Was that a coincidence … or not?
In October, the team’s FERARO study – into the feasibility of Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms – finally got under way after having been on hold since March, along with most other non-Covid-19 essential research,
In this 18-month-long, randomised controlled trial, half of the 80 participants will be given faecal transplants, the other half a placebo, and their progress charted during the following six months.
The results will determine the likely success of a larger, substantive trial.
“We are looking at people with antibiotic resistant bacteria (ARB) in their gut who have also had an invasive infection in the preceding six months,” said Dr Merrick.
“Some people do just have ARB in their gut, but it doesn’t cause a problem. It can be there transiently too, if someone has travelled to parts of the world where it is prevalent, such as the Asian sub-continent.
“But we want to work out how to treat people where it has gone on to cause a problem, perhaps an infection in the urine or bloodstream or biliary system, and then because of the antibiotic resistance, the treatment options are more limited.”
Such patients commonly get locked into a cycle of increasingly unsuccessful treatments until there are no options left.
Dr Merrick said: “There is a cohort that gets stuck in hospital, or keeps coming back with infections that recur because of resistant organisms. It has a massive effect on their lives.
“It is also much more expensive to treat people with ARB. They stay in hospital longer and their outcomes are worse.
“So if we are able to treat the condition and the effects are long-lasting, it will be an important step.”
Currently there aren’t any specific treatments for eradicating ARB, but the hope of the FERARO team is that re-establishing a healthy environment in the gut by repopulating it with bacteria from another individual, will prove to be a viable strategy.
“The big caveat is the availability of the supply of donations from healthy individuals,” he said. “That’s something we are struggling with.”
More altruistic donors who are both willing to go through full health screening and who live within two hours of the hospital are needed.
Time is of the essence before the bacteria in the donations, begin to die, while formulating the subsequent treatment is time-consuming.
Saline solution is added to the stool sample, which is then turned into slurry.
Undigested food is filtered out and then bacteria are pelleted by centrifugation. A cryoprotectant is added and the solution is then freeze-dried and divided up into capsules.
He said: “Faecal transplants have traditionally been delivered either in a liquid solution through a nasal gastric tube or via a tube pushed up the back passage and around to the start of the colon, neither of which is particularly pleasant for the patient.
“And if you have to do that several times over, it’s a big undertaking for the individual concerned and the medical staff.
“You can see the benefits of making a capsule the treatment!”
Ultimately, the team hopes patients “won’t think twice” about what they are taking, although as Dr Merrick says, that remains to be seen.
In the long term, relying on human donations is unlikely to be sustainable. There is too great an input for too little output.
“I think we need to look towards the laboratory manufacture of solutions by trying to mimic what the good things are in the stool donations,” he said.
“That entails identifying exactly what the ‘good things’ are and then what a good, healthy balance of bacteria looks like.”
One anomaly the team is already aware of is the differing patient responses to the donated material.
“We know from when faecal transplant has been used to treat inflammatory bowel diseases that, for some reason, certain donations seemed to be more efficacious than others,” said Dr Merrick. “What we don’t know is why.
“It is likely there is a dependence on the reason for which the transplant was given, because with C.diff. it would appear it doesn’t matter who gives the donation, while with IBD it seems that some donors may be better than others.
“I’m not sure we will be able to find out why with the number of people we have in this study, but ultimately it will be a really important question to answer.”
Anyone interested in talking to the FERARO team about the trial can contact them via email ppi@gstt.nhs.uk.
