Fighting antibiotic resistance with faecal transplants

We’ve learned just how crucial the relationship between us and our gut bacteria is, so you won’t be surprised to hear that, when we do damage to our microbes, we could also be opening the door to health complications.

Antibiotics are used to treat or prevent bacterial infections. But while they can kill bad bacteria, they also do damage to good bacteria too, leaving people vulnerable to being colonised with a pathogen that could make them ill. This problem is often approached with the use of more antibiotics, leading to a vicious cycle with a progressively more deranged microbiome and bacteria that become increasingly antibiotic resistant.

Indeed, the superbugs that develop as a result are seriously bad news. Earlier this year, The UN Environment Programme called antimicrobial resistance a principal public health challenge and suggested as many as 10 million people a year could be dying from these infections by 2050.

So what can we do about it? Michael Woodworth from the Emory School of Medicine thinks part of the answer could lie in transplanting healthy bacteria from one person to another, and has just published some clinical trial results after performing faecal microbiota transplants in kidney transplant patients with established antimicrobial resistance…

Mike - We thought we would conduct a clinical trial to better understand if directly transplanting these whole communities of microbes from healthy people into people who are colonised with these resistant bacteria might be a way to try to reduce colonisation without using more antibiotics.

Chris - How did you do it? We dub this the 'transpoosion', don't we? The whole idea of recolonising people with the right stuff.

Mike - So I conducted this study with Dr. Colleen Kraft, who essentially helped to start the fecal transplant programme at Emory in 2012. We identified one of the stool donors for that programme who was very reliable and was very easy to work with and, in-house, manufactured a number of doses to transplant to kidney transplant recipients who had had a problem with a resistant bacterial infection. Then, we recruited and enrolled 11 participants who were randomised to either start with faecal microbiota transplant, which we call an FMT for short, or to start with an observation period with delayed FMT if they were still colonised with these resistant bacteria after a period of 36 days,

Chris - Just before you tell us what happened, how did you administer the transplant to these people? Did they literally have to swallow this solution?

Mike - That's an area that is still being evaluated. What is the best way to get these microbes in the right place? And in other studies, people have used colonoscopies, people have used nasal feeding tubes. In this study, we used enemas, so we directly instilled the material through patients' bottoms. And the reason for this was that we wanted to minimise the risk for the participants and we didn't want to subject everybody to colonoscopy or potential additional risks of anaesthesia.

Chris - So what happened once you've administered this? Before we talk about the transplanted people, in the people who were watched, did any of them get better on their own? Did they get rid of or kick out the resistant microbes and get back to a more normal microbiome?

Mike - We were surprised that in the five patients that were randomised to start in the observation group, that is, with a delayed FMT, that they were still positive. None of them were culture negative at their last visit. And we're expecting that we might observe a little bit more frequent decolonisation than this when just observing patients, but none of them were negative at their last visit prior to an FMT.

Chris - And how did that compare with the people that you went in at the get go and gave them the FMT. You transplanted the suspension of bugs in.

Mike - When we directly compared the five patients that were randomised to a delayed FMT to the six patients that were randomised to start with an FMT, four out of the six patients that started with an FMT were negative at their last visit compared to none that were randomised to start with observation. And because the dose of FMT that's needed to reduce colonisation is really not known, we set up the study to be able to offer patients a second treatment if they were still positive after one dose. And when we looked across all patients that got at least one FMT in our study, including those that had a delayed FMT after a period of observation, 8 out of 10 patients that were treated with FMT were negative at their last visit.

Chris - Do you know how it's working? Why should just shoving in more microbes into an environment which is already teaming with microbes displace the bad guys in the way that it did?

Mike - Well this is really the work to do. And we have ideas based on some of the analysis that was done in this paper. Some of it we think is similar to what we've seen in patients that have this problem of recurrent C. difficile infection that has been treated the most with FMT. And we think that some patients that are colonised with resistant bacteria really have a very abnormal microbiome. They're very disrupted and they really just don't have a similar amount of the healthy bacteria that we might expect to see in people that are walking around that are not colonised with these resistant bacteria. And those patients responded very quickly when we saw the bacteria from the donor show up in the data from the recipients. Now, on the other hand, there were a lot of patients that were in our study that actually seemed to have a milder set of disruptions in their microbiome. And for these patients it's a little bit less clear and there's more work to be done. But we do think that there are similar changes in what these microbes are doing after FMT that seem like they are doing more activities that are helpful for the hosts and also in reducing the virulence of other bacteria.