The microbiome in everyone is as unique as a fingerprint, and gaining a better understanding of how it contributes to the development of chronic liver disease offers an exciting opportunity to develop new therapeutic avenues. Liver diseases are becoming more prevalent and at the moment the only definitive treatment is liver transplantation. We are moving towards the frontiers of the microbiome and the King’s team are delighted to be part of this journey
Dr Debbie Shawcross
05 March 2019
MICROB-PREDICT - €15 million EU funded microbiome research project kicks off
22 European institutions, including King's, join forces to tackle end-stage liver disease and liver failure with personalised microbiome-based treatment strategies
Researchers from the School of Immunology & Microbial Sciences are part of the 6-year-long EU-funded MICROB-PREDICT project which includes world-leading microbiome experts, technology leaders, clinical specialists, patient organisations (ELPA) and the European Association for the Study of the Liver (EASL). The project aim is to understand how the human microbiome contributes to the development of liver decompensation and acute-on-chronic liver failure (ACLF).
The team from King's is lead by Dr Debbie Shawcross and includes Dr Mark McPhail, Dr Vishal Patel, Dr Saeed Shoaie and Dr David Moyes.
The MICROB-PREDICT consortia
Worldwide, 1.2 million people die of liver cirrhosis every year, and less than 10% of the research in the field is focused on decompensated cirrhosis and acute-on-chronic liver failure (ACLF). It is crucial to develop novel treatments and help affected individuals.
High-quality data of more than 10,000 subjects from three existing EU-funded projects (GALAXY, LIVERHOPE, PREDICT) will be analysed to design novel, microbiome-based tests and diagnostic tools.
The 75-month project aims to develop improved and more personalized therapies for patients suffering from cirrhosis and ACLF.
The fatal course of decompensated cirrhosis & ACLF
End-stage chronic liver disease (cirrhosis) is a major cause of morbidity and mortality and has a large socioeconomic impact because of high health care costs and the patients’ inability to work or seek employment. Patients show symptoms, start suffering, and eventually die of chronic liver cirrhosis when the body essentially can’t compensate the mis- or dysfunctional liver condition any longer. That’s why it’s called decompensated (as opposed to compensated) cirrhosis. Decompensated cirrhosis is defined by the accumulation of fluid in the abdomen (ascites), impaired brain function (hepatic encephalopathy), and often also bleeding in the digestive tract (gastrointestinal haemorrhage). Eventually, it progresses to acute-on-chronic liver failure (ACLF) and death.
Genetic predisposition and/or infections can increase the risk for decompensated cirrhosis and worsen its prognosis. The gut microbiome consists of all bacteria, viruses, parasites, fungi and archaea bacteria that colonize the gastrointestinal tract. Aberrations in the gut microbiome, a damaged gut-body barrier, excess bacteria crossing that barrier (microbial translocation), and systemic inflammation can trigger decompensated cirrhosis and its progression to ACLF. A recent multi-centre study by the European Foundation for the study of Chronic Liver Failure (EF-CLIF, Barcelona) demonstrated that bacterial infections are common precipitating events for ACLF in Western countries, and confirmed the high mortality rate of ACLF.
How patients with cirrhosis and ACLF will benefit from MICROB-PREDICT
MICROB-PREDICT aims to develop personalised, microbiome-based treatment strategies to prevent and treat 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 will integrate 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 comprehensive database will be generated, including data from a stool, blood, saliva, mucosa and urine samples over the course of the disease, allowing for a novel longitudinal analysis, thereby clearly providing added value over the previous studies. MICROB-PREDICT will identify and validate microbiome-based individual biomarkers and predictors of a) healthy, low-risk conditions, b) decompensated cirrhosis and progression to ACLF, and c) treatment response. In addition, the role of environmental factors (e.g. exposure to pollutants), lifestyle (e.g. smoking), diet (e.g. alcohol consumption), comorbidities, ageing, geographic differences and socio-economic factors will also be taken into account.
Gained knowledge will be translated into clinical tests for doctors and every-day tools for liver-disease patients, such as point-of-care (POC) diagnostic tests and state-of-the-art nanobiosensors for smartphone-based patient self-monitoring. MICROB-PREDICT also tries to identify and validate “biomarker signatures” that reliably predict the therapeutic response to treatment with human albumin in a randomized clinical trial (ALB-TRIAL). In short, the 6-year-long project focusses on factual and guided, rather than symptom-based treatment, and aims to develop personalized, effective and well-targeted treatment approaches to reduce the burden on both the patients as well as the health care system.