Why faecal transplants could bring hope to patients with cirrhosis

A landmark trial has shown that a faecal transplant can treat advanced liver disease and fight antimicrobial resistance.

The findings, which were announced at the EASL Congress in Vienna, showed that a faecal microbiota transplant (FMT) can dramatically improve gut health, and provide another much-needed treatment option for patients with advanced cirrhosis (scarring of the liver).

“FMT involves taking a stool from a healthy individual and transplanting it into somebody that has a disease, in this case, liver disease,”  said Dr Lindsey Edwards, co-leader of the study and Honorary Senior Lecturer in the Department of Inflammation Biology at King’s College London.

“From a clinical point of view, we can reduce something called hepatic encephalopathy. This is basically where you have too much ammonia, and this causes problems like brain swelling, which can lead to death. This was reduced during the trial, and we also saw improvements to gut microbes and the gut barrier.

“FMT basically resets the gut microbiome and metabolically reprogrammes the immune system so that it’s better able to deal with infections. Liver patients are particularly prone to infections, so this is really great news,” she said.

Cirrhosis is the most advanced stage of liver disease, and in many cases, a liver transplant is the only definitive treatment option. However, not all patients are eligible for liver transplants and waiting lists can be extensive.

This new treatment option therefore offers a renewed sense of hope for patients with advanced liver disease, and the authors of the study hope the treatment could be rolled out on the NHS, once the results of a larger trial are published.

Faecal transplant trial to be expanded

The new trial, which is launching in the UK, will involve 300 patients with liver disease. The trial differs from the last, as this time, the study sample is much larger (300 participants compared to 32), and half the patients will take capsules of freeze-dried faecal matter – often referred to as ‘crapules’ – instead of having an endoscopy, while the other half will take a placebo.

Thankfully, the ‘crapules’ have none of the taste or smell as the name suggests, and this form of treatment is far less invasive than an endoscopy – benefitting participants.

The participants will receive five capsules of medicine (either FMT or placebo) which are taken at 91-day intervals (every three months) over the course of 21 months.

The new trial allows the researchers to assess participants over a 2 year-period – a much longer period than the previous study, which only followed-up patients for 90 days, allowing for a more detailed analysis of the medicine’s impact.

The stool is taken from a healthy donor who is vigorously screened for bacterial and parasitic infections, Covid-19 and other infections, as well as questioned on risk factors.

Blood, stool and urine samples will be collected at the time of recruitment and then retaken at three, six and 12 months. The samples will then be analysed for various biomarkers such as cytokine production, markers of barrier integrity, global metabolite profile and faecal proteomics.

Could FMT be rolled out on the NHS?

In an exclusive interview with PHT, Dr Edwards explained the potential implications of this new research.

“There are many diseases that start off with a problem with the bugs in your gut,” she said. “This treatment could therefore have a far reaching impact on diseases including Parkinson’s disease, Alzheimer’s disease, rheumatoid arthritis, or really any kind of autoimmune disease.”

However, since the treatment relies on donors, there are questions around how this treatment could be rolled out on a larger scale. To tackle this, Dr Edwards says her team at King’s College London are now working with stakeholders to develop a policy document.

“The treatment involves using stools, something that we flush down the toilet, so it’s not expensive to produce or manufacture. If FMT were to be made widely available, we believe we could work in conjunction with blood donation programmes.

“We’re suggesting that when you donate blood, you donate a stool at the same time. This way, we can build a stool biobank and then select the right donors for the right diseases. We’re now lobbying the government in the UK to build an infrastructure for this.

“Of course, we do have to thoroughly screen the stools, so it’s not something that anyone could do, but it really is a very accessible treatment. It could therefore have a global impact – it has huge promise and huge potential,” Dr Edwards said.

Improving gut health naturally – what about probiotics?

While FMT is still in the early stages of development, there are various other things liver patients – and people more generally – can do to improve their gut health.

Dr Edwards advises patients not to rely on probiotics for improving gut health, and instead suggests making simple diet and lifestyle changes.

“Sadly, probiotics haven’t really lived up to expectations. I think the reason for this is that it’s very difficult for a particular strain of bacteria to engraft – when they colonise the gut and have beneficial effects – because that particular strain will have to compete with thousands of other bacteria. Probiotics also struggle to get past your stomach acid, so often, they never actually reach the gut.

“FMT is different because it is already a stable community of bacteria that is fully developed and has reached harmony with one another. We’re currently doing work to discover what the ‘magic ingredients’ are so that we don’t have to give a stool, but we have a long way to go before we discover that, I think.”

To improve gut health, Dr Edwards instead suggests that patients make simple changes to their diet, such as incorporating live culture yoghurt into their eating regime. She also suggests reducing sugar and alcohol consumption, and eating more complex carbohydrates.

“There absolutely needs to be more awareness about the importance of diet and good gut health. We’re currently doing some policy work with the UK government on this.

“If we were to educate children at school about the importance of a healthy diet, eating live culture yoghurts and things like this, then we would prevent a lot of these people from going on to develop diseases later in life.”