The Shawcross Lab is led by Professor Debbie Shawcross
Chronic liver disease is increasing on a global scale and patients are vulnerable to developing infections and death. The main aim of the lab is to characterise the immune-gut-liver-brain axis in patients and to develop interventions which normalise the abnormal gut microbiome reducing the development of complications and liver failure.
People
Principal Investigator and Lecturer (Adj/Hon)
PhD Student
Professor of Hepatology and Chronic Liver Failure
Projects
MICROB-PREDICT [825694] MICROBiome-based biomarkers to PREDICT decompensation of cirrhosis and treatment response
MICROB-PREDICT aims to develop personalised, microbiome-based treatment strategies to prevent and treat decompensated cirrhosis and acute-on-chronic liver failure (ACLF) and reduce mortality by investigating the human gut microbiome. The goal is to identify predictors and mechanisms associated with the development of decompensated cirrhosis and its progression to ACLF. The need for personalised treatment strategies becomes apparent when considering that there are substantial, yet still largely unexplained, individual differences in developing decompensated cirrhosis and ACLF. At the same time, this observation bears the chance for more effective, more individualised and more targeted treatments. The pan-European research project is integrating microbiome results and other patient data from previous large-scale studies, such as GALAXY, LIVERHOPE and PREDICT, combining more than 200,000 data points from about 10,000 subjects.
A PROspective, randomised placebo-controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis - PROFIT Trial
Patients with advanced cirrhosis have enteric dysbiosis with small bowel bacterial overgrowth and translocation of bacteria and their products across the gut epithelial barrier. This culminates in systemic inflammation and endotoxemia which induces innate immune dysfunction predisposing to infection and development of complications such as bleeding, sepsis and hepatic encephalopathy. It also plays a key role in the natural history of cirrhosis by influencing the rate of progression to advanced liver disease and terminal liver failure. The investigators propose an intervention utilising Faecal Microbiota Transplantation (FMT) from a healthy donor to modify the gut microbiome alleviating gut dysbiosis and immune dysfunction. This may ultimately reduce the progression to chronic liver failure and the development of infection and organ dysfunction. The primary objective of this study will be to assess whether stabilising gut dysbiosis with FMT in patients with advanced cirrhosis is both feasible and safe.
National Institutes of Health - InTeam Consortium- Integrated Approaches for Identifying Molecular Targets in Alcoholic Hepatitis Human Biorepository Core
Purpose: To improve the diagnosis and assessment of severity of acute alcoholic hepatitis Participants: Patients admitted to one of ten centres with acute alcoholic hepatitis Procedures (methods): Consecutive patients admitted with acute alcoholic hepatitis will be enrolled in an NIH U01 study of acute alcoholic hepatitis where liver tissue, blood and stool will be collected to discover and validate factors associated with diagnosis, severity of disease and survival.
The PROMISE trial
The PROMISE trial is led by Professor Shawcross at King’s College London and co-sponsored by King’s College Hospital NHS Foundation trust. The £2.5 million trial is funded by a National Institute for Health and Care Research (NIHR) and Medical Research Council (MRC) partnership. It will recruit 300 patients with liver cirrhosis across the UK to test whether oral Faecal Microbiota Transplant (FMT) capsules from freeze-dried stool from healthy volunteers reduces the likelihood of getting an infection. Infections in people with cirrhosis are often severe and can be fatal. People with cirrhosis have an unhealthy gut microbiome with an increased number of ‘bad’ bacteria in the bowel which makes them highly susceptible to a host of infections. Professor Shawcross has shown in a smaller trial called the PROFIT trial that replacing the unhealthy gut microbiome with a healthy one from healthy volunteers in a process known as FMT is safe and efficacious.
Publications
Awards
- Partner [KCL PI] in EU Horizon 20:20 MICROB-PREDICT [825694] MICROBiome-based biomarkers to PREDICT decompensation of cirrhosis and treatment response – April 2019-2024 - €15 million awarded].
- NIHR Research for Patient Benefit (RfPB) Programme Grant [PB-PG-0215-36070]: A PROspective, randomised placebo-controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis - PROFIT Trial – Jan 2018 – Dec 2019.
- King’s Together Award - To set up the UK’s first GMP-compliant and MHRA licensed manufacturing unit for faecal microbiota transplantation at King’s College London to facilitate multidisciplinary research and clinical trial activity.
- Evaluation of Mechanism and Efficacy (EME) [NIHR130730]: A PROspective double-blind placebo-controlled multicentre trial of faecal MIcrobiota tranSplantation to improve outcomEs in patients with cirrhosis - PROMISE trial – May 2021-2026 - £2,575,994
News
MPs invited to get their livers checked by researchers
Expert researchers and clinicians have been raising awareness about the importance of liver health in Parliament by hosting a liver screening event for MPs.
King's hosts antimicrobial resistance awareness event at Westminster
On Tuesday 22nd March, King’s hosted the event Tackling Antimicrobial Resistance in Liver Disease in the Churchill Rooms at the Houses of Parliament.
PhD students
Dr Charlotte Woodhouse (Clinical Research Fellow and PhD student)
Dr Thomas Tranah (Clinical Research Fellow and PhD student)
People
Principal Investigator and Lecturer (Adj/Hon)
PhD Student
Professor of Hepatology and Chronic Liver Failure
Projects
MICROB-PREDICT [825694] MICROBiome-based biomarkers to PREDICT decompensation of cirrhosis and treatment response
MICROB-PREDICT aims to develop personalised, microbiome-based treatment strategies to prevent and treat decompensated cirrhosis and acute-on-chronic liver failure (ACLF) and reduce mortality by investigating the human gut microbiome. The goal is to identify predictors and mechanisms associated with the development of decompensated cirrhosis and its progression to ACLF. The need for personalised treatment strategies becomes apparent when considering that there are substantial, yet still largely unexplained, individual differences in developing decompensated cirrhosis and ACLF. At the same time, this observation bears the chance for more effective, more individualised and more targeted treatments. The pan-European research project is integrating microbiome results and other patient data from previous large-scale studies, such as GALAXY, LIVERHOPE and PREDICT, combining more than 200,000 data points from about 10,000 subjects.
A PROspective, randomised placebo-controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis - PROFIT Trial
Patients with advanced cirrhosis have enteric dysbiosis with small bowel bacterial overgrowth and translocation of bacteria and their products across the gut epithelial barrier. This culminates in systemic inflammation and endotoxemia which induces innate immune dysfunction predisposing to infection and development of complications such as bleeding, sepsis and hepatic encephalopathy. It also plays a key role in the natural history of cirrhosis by influencing the rate of progression to advanced liver disease and terminal liver failure. The investigators propose an intervention utilising Faecal Microbiota Transplantation (FMT) from a healthy donor to modify the gut microbiome alleviating gut dysbiosis and immune dysfunction. This may ultimately reduce the progression to chronic liver failure and the development of infection and organ dysfunction. The primary objective of this study will be to assess whether stabilising gut dysbiosis with FMT in patients with advanced cirrhosis is both feasible and safe.
National Institutes of Health - InTeam Consortium- Integrated Approaches for Identifying Molecular Targets in Alcoholic Hepatitis Human Biorepository Core
Purpose: To improve the diagnosis and assessment of severity of acute alcoholic hepatitis Participants: Patients admitted to one of ten centres with acute alcoholic hepatitis Procedures (methods): Consecutive patients admitted with acute alcoholic hepatitis will be enrolled in an NIH U01 study of acute alcoholic hepatitis where liver tissue, blood and stool will be collected to discover and validate factors associated with diagnosis, severity of disease and survival.
The PROMISE trial
The PROMISE trial is led by Professor Shawcross at King’s College London and co-sponsored by King’s College Hospital NHS Foundation trust. The £2.5 million trial is funded by a National Institute for Health and Care Research (NIHR) and Medical Research Council (MRC) partnership. It will recruit 300 patients with liver cirrhosis across the UK to test whether oral Faecal Microbiota Transplant (FMT) capsules from freeze-dried stool from healthy volunteers reduces the likelihood of getting an infection. Infections in people with cirrhosis are often severe and can be fatal. People with cirrhosis have an unhealthy gut microbiome with an increased number of ‘bad’ bacteria in the bowel which makes them highly susceptible to a host of infections. Professor Shawcross has shown in a smaller trial called the PROFIT trial that replacing the unhealthy gut microbiome with a healthy one from healthy volunteers in a process known as FMT is safe and efficacious.
Publications
Awards
- Partner [KCL PI] in EU Horizon 20:20 MICROB-PREDICT [825694] MICROBiome-based biomarkers to PREDICT decompensation of cirrhosis and treatment response – April 2019-2024 - €15 million awarded].
- NIHR Research for Patient Benefit (RfPB) Programme Grant [PB-PG-0215-36070]: A PROspective, randomised placebo-controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis - PROFIT Trial – Jan 2018 – Dec 2019.
- King’s Together Award - To set up the UK’s first GMP-compliant and MHRA licensed manufacturing unit for faecal microbiota transplantation at King’s College London to facilitate multidisciplinary research and clinical trial activity.
- Evaluation of Mechanism and Efficacy (EME) [NIHR130730]: A PROspective double-blind placebo-controlled multicentre trial of faecal MIcrobiota tranSplantation to improve outcomEs in patients with cirrhosis - PROMISE trial – May 2021-2026 - £2,575,994
News
MPs invited to get their livers checked by researchers
Expert researchers and clinicians have been raising awareness about the importance of liver health in Parliament by hosting a liver screening event for MPs.
King's hosts antimicrobial resistance awareness event at Westminster
On Tuesday 22nd March, King’s hosted the event Tackling Antimicrobial Resistance in Liver Disease in the Churchill Rooms at the Houses of Parliament.
PhD students
Dr Charlotte Woodhouse (Clinical Research Fellow and PhD student)
Dr Thomas Tranah (Clinical Research Fellow and PhD student)
Our Partners
The Francis Crick Institute
European Union
MICROB-PREDICT
