Short summary

Chronic liver inflammation causes formation of fibrotic tissue, which is the precursor to cirrhosis and chronic liver failure. We hypothesize that the gut microbiota plays a crucial role in those individuals who develop fibrosis and those who do not. In this project the participant will undergo an acute alcohol challenge which increases gut permeability and inflow of bacterial products to the liver. Prior to and after the intervention we will collect biological material including blood samples from the liver vein, liver biopsy and feces which will be analyzed using multi-omics techniques to describe the dynamic changes in the gut and liver under alcohol challenge.

Rationale

Chronic liver inflammation causes formation and accumulation of fibrotic tissue. The condition is called liver fibrosis, which is the precursor to cirrhosis and chronic liver failure. Two of the most common etiological factors associated to liver fibrosis are alcohol overuse and the metabolic syndrome.  Traditionally fibrotic liver diseases are classified according to the etiology. Alcoholic liver disease (ALD) must be suspected if the consumption of alcohol excess >30 g/day whereas non-alcoholic fatty liver disease (NAFLD) occurs in patients with no prior history of alcohol overuse and NAFLD is often associated to metabolic syndrome and type 2 diabetes. However, the pathophysiology leading to inflammation and fibrosis is not completely understood, but ALD and NAFLD share some key characteristics. In both diseases the majority of the group at risk (i.e. people with an alcohol overuse or metabolic syndrome) has a fatty liver without inflammation or liver fibrosis, a condition which itself is considered as harmless. In contrast, a smaller proportion has chronic liver inflammation initiating the fibrogenesis. The cause of the inflammation in ALD and NAFLD has not been described in details, but much indicates, that the gut microbiota and the communication with the liver play important roles in those individuals who develop fibrosis and those who do not. The link between the gut and the liver includes evidence that ALD and NALFD are each independently associated to changes in the gut microbiota and increased intestine permeability and translocation of harmful substance from the gut to the liver.

Following an acute alcohol challenge higher levels of bacterial products can be measured in the peripheral vein system. Animal models support that this mechanism may be, that an acute alcohol challenge leads to increased gut permeability and translocation of bacterial product through the portal vein system to the liver.

In this study we will use an acute alcohol challenge to increase the gut permeability and provoke a bacterial translocation from the gut to the liver in order to describe the communication between the gut and liver.

Description of the cohort

We plan to include a total of 40 participants of which 15 participant are diagnosed with alcoholic liver disease, 15 with non-alcoholic liver disease and 10 healthy controls.

Data and biological material

Biological material

• Blood samples from liver vein
• Blood samples from periferal vein
• Liver biopsy
• Faeces
• Saliva
• Urine

The biological material will be analyzed using multi-omics techniques to describe the dynamic changes in the gut and liver under alcohol challenge. 

Questionnaires

• Alcohol habbits and history
• Medical history
• Dietary diary

Other data

• Age, gender, weight, height

Collaborating researchers and departments

Department of Clinical Biochemistry and Pharmacology, Odense University Hospital

Department of Pathology, Odense University Hospital

• Associate Professor Sönke Detlefsen

Novo Nordisk Center for Basic Metabolic Research, University of Copenhagen

• Professor Torben Hansen

European Molecular Biology Laboratory, EMBL, University of Heidelberg, Germany

• Postdoctoral fellow Shinichi Sunagawa

Biomedical Research Foundation, Academy of Athens, Greece

• Foteini Christodoulou

Center for Protein Research, University of Copenhagen

• Professor Matthias Mann

Steno Diabetes Centre A/S

• Professor Matej Oresic

Nordic Biosciense A/S

• CEO and professor Morten Karsdal

Laboratory for Fibrosis and Portal Hypertension, Department of Internal Medicine, University of Bonn, Germany

• Associate Professor Jonel Trebicka