Tackling antibiotic resistance in people with chronic liver disease: could a poo transplant be the answer?

Posted on: 22nd March 2022

PROMISE – Fecal Microbiota Transplant (FMT) Trials (fmt-trials.org)

Bacterial infections are a serious problem for people who have liver cirrhosis – especially if the infection is resistant to antibiotics and cannot be treated.

The British Liver Trust is supporting an exciting new research project that is being led by clinicians and scientists at King’s College London. Professor Debbie Shawcross, who leads the team, explains more about the project, what poo transplants are and how they might help people with liver disease in the future.

What is this research trying to do?

This research study looks at whether giving Faecal Microbiota Transplants (or poo transplants) to people with liver disease can clear up infections that are resistant to antibiotics.

Antibiotics are one of the greatest medical achievements of the 20th century. They play an important role in modern medicine. Without them, we couldn’t carry out complicated treatments like surgery and chemotherapy because the risk of infection would be too high. But the number of bugs that are resistant to antibiotics is growing. And that’s a big problem.

Drug-resistant bacteria have developed ways to defend themselves so they cannot be killed by an antibiotic. Bacteria can be resistant to just one antibiotic, or to many different ones. Because these resistant bacteria are harder to treat, people develop long-running infections and can become seriously ill or even die. Infections that last longer are also more likely to spread to other people – this can lead to serious issues in places like hospitals.

Already drug-resistant infections cause over half a million deaths every year worldwide and the number is growing. Finding new, effective ways to treat resistant bacteria is one of the most important challenges in medicine. This means that this exciting research may have implications far beyond liver disease.

Professor Shawcross explains, “Liver disease patients are particularly vulnerable to drug resistant bacteria. A recent published study revealed that among London  patients with cirrhosis who were presenting with liver failure, almost 30%  had infections resistant to conventional antibiotics. So, it’s really important we find a solution to this problem.”

What’s a poo transplant?

First things first, poo transplants are not nearly as disgusting or outlandish as they might sound. They have been a hot topic of medical research for decades. They are licensed in several countries including the UK for treatment of Clostridium difficile infection that keeps coming back.

The point of a poo transplant isn’t the poo itself. It’s the helpful bacteria that we should all have living in our bowel, known as our microbiota, that are also present in our poo. They live in our bowel naturally, in balance with our bodies. And they help us do many different jobs, from breaking down food to building a strong immune system.

Some things, including long-lasting infections and conditions such as cirrhosis, upset this balance. They interfere with the helpful bacteria and can kill them off. Poo transplants are a way of adding helpful bacteria from a donor back into the bowel. This helps get the bowel back in balance and can clear up infections by replacing the harmful bacteria that cause them.

It’s important to make sure that poo donors are healthy and no infections could be passed on. Both the donor and the sample are screened for a wide variety of conditions in the same way that all organ and blood donors are screened.

What has bacteria got to do with liver disease?

Although most people’s liver disease isn’t caused by bacteria in the first place, they play a key role in the complications of cirrhosis and how quickly it progresses. Cirrhosis upsets the balance of helpful bacteria, especially in the small bowel. This puts people with cirrhosis at the centre of a network of risks linked to bacterial infections.

Firstly, people with cirrhosis have too many bacteria growing in their small bowel. This can lead to the waste products of the bacteria and even the bacteria themselves leaking out into the bloodstream and elsewhere. In turn, this causes problems more widely such as a weakened immune system and complications including hepatic encephalopathy which affects normal brain functioning and short term memory.

People with cirrhosis are also more prone to catching infections. Not only can these infections be serious themselves, they too can trigger further complications such as hepatic encephalopathy.

Regular courses of antibiotics help keep bacteria under control and treat outbreaks of infection. But we now know that the more antibiotics you take, the higher the risk of developing a drug-resistant bacterial infection which will no longer respond to antibiotics. Because people who have these infections usually need hospital treatment, you are also more at risk of catching a drug-resistant infection in hospital. And people with cirrhosis are likely to have to spend time in hospital as a result of complications, so they are at higher risk of catching a drug-resistant infection.

Put simply, cirrhosis causes an imbalance of bowel bacteria which means that people are more likely to develop drug-resistant bacterial infections. And poo transplants hold the promise of shifting bowel bacteria back into balance without the major drawback of antibiotic resistance.

What will this new research find out?

Professor Shawcross aims to show that poo transplants can clear up drug-resistant infections in people with cirrhosis. Her team have already run a small pilot study with 32 people known as the PROFIT Trial. This showed that poo transplants are safe for these patients and that enough people meet the criteria for having one and will agree to the procedure.

The early research also found that 1 in 5 of the people who took part had a drug-resistant bacterial infection. The scientists took samples from all the patients before they had any treatment and after one week, one month and three months. The scientists are now going to test these samples to see if having a poo transplant had any effect on having a drug-resistant bacterial infection.

The next stage is a new research project, the PROMISE Trial, that will see if patient can be treated with a poo capsule. Patients will be given a similar dose of bugs as in the PROFIT study (equivalent to 80g of poo). But this will be in the form of 5 capsules. The capsules look just like any other medicine. They don’t taste of anything and they have a special coating that means they won’t breakdown until they get into your bowel, which is where the bugs are needed.  Over two years patients in the new PROMISE trial will get 5 capsules every three months at their outpatient appointments.

If this research shows that poo transplants are an effective way to treat drug-resistant infections in people with cirrhosis, Professor Shawcross hopes this would be the first stage of making them part of the standard treatment.

The British Liver Trust is helping the researchers find out patients’ views on using poo transplants in this way so that any barriers to an effective treatment can be understood and overcome.

What are the wider implications?

If the research is successful, this could have implications for other areas of healthcare. Poo transplants or Faecal Microbiota Transplants could be used as a strategy to avoid antibiotic use in other chronic disease conditions. The British Liver Trust is working with the research team to raise awareness amongst MPs and policy makers.  Once the new results are ready, a roundtable meeting will be held to share their findings and discuss what other questions need to be answered before poo transplants could be rolled out as a treatment in the NHS.

This would be a big step forward for the treatment of infections in the UK. Professor Shawcross has her sights on another liver disease-specific goal as well. She believes that poo transplants could hold the key to managing cirrhosis. And that by rebalancing the bowel’s bacteria the procedure would take away the trigger for complications such as hepatic encephalopathy. It’s a powerful idea, especially as many more people would be able to benefit compared to a liver transplant. And while we aren’t there yet, this research could be a crucial step on the way.

 

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