Gut microbiota and host response in liver diseases
Research type
Research Study
Full title
Assessment of Microorganisms and host response In Liver Diseases (MILD Study)
IRAS ID
324543
Contact name
Indrani Mukhopadhya
Contact email
Sponsor organisation
University of Aberdeen
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
The study aims to elucidate the role of the gut microbiota and host immune response in liver disease through three work packages as described below:
Work Package 1: Investigation of the alteration of gut microbiota in liver diseases.
The gut-liver axis is an important factor in the development and progression of a wide spectrum of liver diseases including alcohol related liver disease, non-alcoholic fatty liver disease, immune mediated liver diseases (autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis), viral hepatitis and cirrhosis. Alterations in the composition and characteristics of gut microbiota, comprising of bacteria, fungi, and viruses, have been demonstrated in several of these conditions. However, the exact pathways starting from this alteration in the gut to development of disease in the liver has not been clearly elucidated. Additionally, several liver diseases lead to disruption of the gut barrier function and translocation of bacteria leading to life threatening complications. Our aim is to define the changes in microbial composition in the gut and assess its aetiological role in liver diseases. This will involve identification and isolation of microbial strains that are associated with these conditions. Additionally, we will characterise the aberrant metabolic pathways e.g., bile salt, alcohol, short chain fatty acid metabolism etc. that are initiated by this altered microbiota. This study will identify newer gut microbiota-modulating agents as personalized treatment options for liver diseases and its complications.Work package 2: Assessment of host response to specific gut microbes in liver diseases.
Changes in the composition of the gut microbiota leads to abnormal metabolites reaching the liver which in turn affects hepatic immunity and inflammation. We will assess the host response against the specific pathogens by investigating recruitment of inflammatory cells in response to microbial stimuli, changes in gene expression, and upregulation of proinflammatory mediators. Our specific focus is to elucidate how the altered microbiota triggers an aberrant response in immune cells involved in recognition and clearance of pathogens. This will help identify novel therapeutic approaches, such as targeting specific immune cells or pathways that can reverse the pathogenic processes.Work package 3: Characterise the changes in the liver immune microenvironment by analysing liver biopsies from patients.
The alterations in the gut microbiota in liver diseases can lead to disruption of the gut barrier function and translocation of microbial metabolites through the portal circulation to the liver. We will study the host immune cell signatures and their corresponding location by analysing biopsies from patients with liver disease in a subset of patients. Using newer molecular techniques we will decipher heterogeneity, differentiation, and intercellular immune crosstalk at the single-cell level in the liver which will also help localise the regional alteration of immune and metabolic dysfunction.REC name
South Central - Oxford C Research Ethics Committee
REC reference
24/SC/0103
Date of REC Opinion
26 Mar 2024
REC opinion
Favourable Opinion