Advancing liver health through microbiome research

Dr Benjamin Mullish

On World Liver Day, Dr Benjamin Mullish from the Department of Metabolism, Digestion and Reproduction, discusses the research being done on the microbiome and faecal (or ‘intestinal’) microbiome transplants (FMT), and how he hopes that can be converted from ‘bench to bedside’ to improve the lives of patients with liver conditions. 

When most of us hear the words ‘gut bacteria’, we think about germs that can cause infection and make people ill.  However, more recently, scientists and doctors have recognised that we also have billions of ‘beneficial’ bacteria (and other microbes) in our gut that play important roles in keeping us healthy.   The specific ‘mix’ of microbes that a person has in their gut, and the environment in which they live – now often called the gut microbiome – is distinct between different people like a fingerprint.  Furthermore, the gut microbiome is influenced by and altered by a number of factors, including our diet, our medications (particularly antibiotics), and how old we are.

Of further interest, we now think that our gut microbiome plays an influence over our vulnerability to developing a range of medical conditions, how the condition progresses if we do develop it, and even how well we might respond to different treatments used for the condition.  This includes a number of different liver diseases; the gut and the liver are very close physically within the body, and the gut microbiome seems to be an important factor that impacts upon how these two organs ‘talk to’ each other in health and disease.  Within the Section of Hepatology and Gastroenterology, one of our major areas of research relates to how an altered gut microbiome may contribute to different liver diseases, and whether we might be able to alter the gut microbiome as a new approach to treating them.

As an example of the sort of work that we do, one important recent study involved collecting blood, urine and poo samples from nearly 300 patients with , formerly known as Non-alcoholic Fatty Liver Disease, and using cutting-edge experimental techniques to explore how the gut microbiome differs between people with less severe and more advanced versions of the condition.  In particular, we were able to use the unique metabolomics (the study of all the metabolites present in cells, tissues, and organs) expertise of the MRC-NIHR BRC National Phenome Centre to identify in much greater detail than had been previously shown how a large number of chemicals produced by our gut bacteria may be linked to how MASLD progresses.  Furthermore, we were also able to use cell culture experiments to show how the level of ‘leakiness’ of the gut wall alters depending upon the severity of the condition.  Research like this aims to give us new insight into the cause of MASLD, to help us develop improved biomarkers (a substance whose detection indicates a particular disease state or a response to a therapeutic intervention) for the condition and may also suggest new approaches to treat the condition.

If having a particular gut microbiome affects your risk of developing or outcome from a liver disease, then could altering your gut microbiome be a new way of treating the condition?  One dramatic way of trying to change your entire gut microbiome is using an approach called ‘faecal (or ‘intestinal’) microbiome transplant’.  This involves:

  • Taking a poo sample from a healthy ‘donor’ (who has undergone health screening with questionnaires and laboratory tests);
  • Processing their samples in a laboratory to prepare a mixture containing the ‘beneficial’ bacteria, and;
  • Transferring this into the gut of an infected patient.

This approach has been shown in trials to be a highly effective way of treating a particular gut infection (called C. difficile infection; CDI) that occurs in people with a damaged gut microbiome. FMT has been performed at Imperial College Healthcare NHS Trust for almost ten years and has been found to be both safe and effective.  In fact, doctors at Imperial have been some of the key contributors to the updated national guidelines on FMT that have just been published.  Given that FMT is so effective for CDI, there is great interest as to whether FMT might hold promise in treating other conditions related to the gut microbiome; at Imperial, we are currently involved in a number of studies investigating FMT in potentially treating a range of different liver conditions.

Building upon successful outcomes from an earlier ‘pilot’ study, we are collaborating with a team at King’s College London on a clinical trial that they are running called PROMISE, looking at the impact of FMT upon clinical outcomes in patients with cirrhosis – scarring of the liver caused by long-term liver damage.  Imperial is recruiting patients to and analysing samples from a trial of FMT that is soon to begin in people with a rare liver condition called primary sclerosing cholangitis.  Led by Dr Penny Manousou, we have performed a small study ourselves of using FMT in people with MASLD, and have started to see some promising signals of how this might act.  Furthermore, we have recently had funding confirmed from the NIHR EME programme that will enable to us undertake the largest trial to date, involving a number of different hospitals nationally, investigating the potential role for FMT in treating very sick hospitalised patients with a severe form of liver failure related to alcohol use (called alcoholic hepatitis) for which there are currently only few effective treatments.

This area of research is rapidly growing and moving forwards.  As such, we were honoured to recently host a meeting supported by the European Association for the Study of the Liver (EASL), looking at the gut microbiome in liver disease.  We were able to welcome colleagues from across the world to the St Mary’s Hospital Campus of Imperial, allowing us to learn from colleagues spanning many countries who are interested in this area, and hopefully sharing our knowledge and experience with them as well.

In conclusion, within only a few years, the gut microbiome has hugely exploded in terms of interest and research.  Liver disease is one of the areas where this is of closest focus, and where we hope that the close working relationships between scientists and clinicians at Imperial will enable us to stay at the forefront of scientific breakthroughs and trial results.  On World Liver Day, our ultimate hope is that we will be able to convert this knowledge from ‘bench to bedside’, and in doing so improve the lives of our patients with liver conditions.