NICE recommends faecal microbiota transplant

Normally the population of microbes exist in a balanced state it our guts that keeps us healthy. No one species of microbes dominates, and all of them compete for space and nutrients in the environment of the intestine. But not all of these microbial freeloaders have our best interests at heart, and if something happens to upset the apple cart - like we’re exposed to big doses of antibiotics - But when bad bugs outcompete the good guys, they can trigger a vicious cycle that can be hard to break. Ellie Percival had this happen to her. Clostridium difficile - or c. diff - is an infection caused by a bacterium that hijacks the gut and overgrows the normal microbes we rely upon for good health. When the density of bacteria increase, they secrete a toxin that injures the lining of the intestine, causing relentless diarrhoea and bowel injury. It is normally treated with antibiotics - essentially killing off the harmful bacteria and allowing the resident flora to respawn. But for 20-30% of patients, as soon as the treatment ends, the infection occurs over and over again, sometimes at the cost of the patient’s life. Thankfully, for these individuals, there is a treatment which has a whopping 90% cure rate: a faecal microbiota transplant, or FMT. Nibil Quarashi, clinical lead of the Microbiome Treatment Centre at University Hospitals Birmingham, explained to Julia Ravey exactly what FMT is…

Ellie - I'd say my quality of life was just awful. I think in the space of maybe six months, I had been admitted into hospital three times for a total of about two and a half months. And then the whole C. diff came about by literally just having a course of antibiotics due to a sinus infection. So every time the C. diff was treated with the antibiotics, which is just the kind of standard treatment that they'll give patients, I just felt completely paralyzed by the fear of it coming back. It's going to the toilet constantly, like 20 times a day. So it just completely drains you and another symptom of C. diff is your entire colon gets really inflamed and angry. So the pain from just having inflammation is extremely painful. So it's just really unmanageable to live with because I think I'd have about maybe an eight week period of being symptom free and then it would obviously come back again.

Nibil - What it is, is very healthy stool acquired from stringently screened donors, and it's processed in a lab and it's given either via up an NGI route, which is basically where you put a tube that goes through the nose, into the stomach, and it's infused directly into the patient's stomach or the small bowel, or it can be given either as enema or is given through a colonoscopy.

Julia - And what is the healthy stool actually doing there?

Nibil - It is potentially a million dollar question, because if you knew what the answer was, then if you wouldn't be using FMT anymore, you'd be using those components in stool that will cause the same effect that FMT does. So what you're trying to achieve here is you're associating a change in the gut microbiome with the disease. You're trying to potentially reverse that by changing the gut microbiome in very crude fashion, by giving them processed stool from a healthy screened individual, with the aim that if you change the microbiome, maybe the process that leads to that disease also changes. And therefore you're able to treat that disease that way.

Julia - Are there any other conditions where FMT has been shown to be potentially beneficial to patients?

Nibil - There are 80 or 90 conditions where FMT has been explored in clinical trials, but surprisingly, well not so surprisingly actually, none of them have been as promising as they have been for C. diff. C. diff is a very different disease though. It's where you get a field effect where the microbiome looks very different and there are potentially some mechanisms around bile acids, and them being abnormal links to C. diff. The strongest contender really is a condition called ulcerative colitis. This is a condition of the colon, the large bowel, which gets inflamed as a result of an immune mediated condition. Nearly 10 clinical trials have shown that FMD appears to be fairly effective in treating this condition. You've got a cure or remission treatment rate of about only 30 to 40%. And the treatment rate is not sustained. So over time, your microbiome in that patient with ulcer colitis returns back to their abnormal baseline and the disease comes back as well. So it's not a cure.

Julia - And a common condition that many people have is IBS. Could FMT potentially be used in IBS?

Nibil - The IBS is another condition that FMT has been exploded in. There have been at least four clinical trials. The problem with IBS, it's a very heterogeneous condition. So everyone's IBS is different. Some patients have got very mild IBS with a bit of bloating, whereas others will have debilitating diarrhea and abdominal pain. And because of this heterogeneous condition, what these trials do is they lump everyone together into the same group. Even though potentially they might be different syndromes on their own. FMT appears to be effective in some of these trials, but not in the others. There may be a role for FMT in IBS, but again, there might be a very small court of patients or a subgroup of patients in this massively heterogeneous condition.

Julia - What do you think the future of FMT is? Do you think we'll still be using this technique 20, 30 years down the line, or do you think research will allow us to find the components of whatever is in that healthy stool? And we can just give that to patients with C. diff instead, or other patients as well with different conditions and we can find the points in the stool that are the things that are doing the job and making things better for them?

Nibil - The problem with FMT is it's a very crude way of treating a condition. Every stool is different. Every stool we obtain from a donor is different. There's no way of standardizing FMT. So every treatment we give a patient is different. Unlike a pill in a lab where, you know, exactly know what chemical formula there is in the pill, you know the exact concentration and you know you can control it. And the other reason is there is no way scaling it up. Our donor pass rate at the Microbiome Treatment Center in Birmingham is only 5%. And if you think about treating chronic diseases where you have hundreds of thousands of patients suffering from it, you need to be able to scale up your donors. And you can't do that because donors are limited, which is why I think the future of FMT is outside treating C. diff. We are using FMT to understand what we are doing to a disease to disease mechanisms that leads to a favorable change, a favorable outcome. So if you are able to understand by introducing X, Y, and Z bacteria or metabolites in that individual with that disease, you're able to change that disease. Maybe the solution is we isolate those bacteria in a lab and grow them up. We can control the concentration, we can control exactly what strains there are. And then we do a clinical trial with those bacteria, or metabolites, to see whether they give you the same effect that FMT does. COVID made all the FMT lab shut down because we know we could detect COVID in the stool and you need to know the pandemic to stop manufacturing again. And for that reason, I don't think the future of FMT for treating chronic diseases is there. I think for C. diff it does have a role, but for other diseases the field is moving towards what we call next generation microbiome therapies.

Julia - And Ellie, who we heard from, had a faecal transplant earlier this year for her C. diff infection, and this is how it impacted her…

Ellie - The procedure kind of completely transformed my life as I'm now, I think, about eight months post transplant, and I've had no signs at all of the C. diff returning. It's just completely given my life back without that constant anxiety of it returning, and now I can actually enjoy life. So, yeah, it's nice. It was about three days later that I noticed a dramatic change in the symptoms. I think before I actually had the transplant, I was going to the loo about 20 times a day. And I think by day three, post transplant, I think I was maybe going three times. So yeah, it was a huge difference. Prior to the FMT, I don't think I'd ever seen such a dramatic change when I was being treated with just the standard antibiotics. I mean, obviously with COVID and everything, holidays have been delayed previously, but I've actually managed to go away and not have the fear of traveling and having to deal and manage all the symptoms. Yeah. It's just, it's not a constant fear. It's nice to live as normal a life as possible, which is great. I'd say FMT is just completely life changing and I'd a hundred percent recommend to anyone with recurrent C. diff.