EMITTIC: The Enteric Microbiome as a Therapeutic Target in Cirrhosis
Research type
Research Study
Full title
The faecal microbiome as a therapeutic target for restoring unconventional T cell immunity in cirrhosis
IRAS ID
255103
Contact name
Debbie Shawcross
Contact email
Sponsor organisation
King's College London
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
The proportions of ‘good’ and ‘bad’ bacteria in the gut are key to remaining healthy and become unbalanced in patients with chronic liver disease (CLD). This causes the gut to become more 'leaky' with bacteria escaping into the bloodstream, causing activation of the immune system which becomes exhausted and is then unable to fight infection. In patients with CLD, disruption of the immune system resulting in susceptibility to infection is a common complication; these infectious events are often severe, frequently resulting in hospitalisation and death despite best medical care. New treatments to restore immunity in cirrhosis are urgently needed.
We hypothesise that recently described unconventional T cells (a population of immune cells) are key mediators of abnormal interactions between the gut bacteria and the host immune system in cirrhosis and that their functions can be modified by transplanting healthy gut bacteria [faecal microbial transplantation (FMT)] to restore a healthy balance. We aim to define the mechanisms by which gut bacteria control the function of key immune cell populations in CLD and to assess the role of FMT and other therapeutic interventions as treatments to restore immune cell function.
We propose an observational study of protocolled collections of patient blood, stool, saliva and urine before and after starting licensed and investigational therapies including b-blockers and rifaximin-α (a non-absorbable antibiotic licensed for end stage chronic liver disease with hepatic encephalopathy). We will generate a biobank to perform ‘state of the art’ analysis of the gut microbiome and its products of metabolism and better understand the imbalance of bacteria in the gut in CLD and its impact on host immune function. In undertaking this project we will combine a collaborative team of academic leaders in the fields of hepatology, immunobiology and bioinformatics.
REC name
London - South East Research Ethics Committee
REC reference
20/LO/0135
Date of REC Opinion
17 Feb 2020
REC opinion
Unfavourable Opinion