Short summary

The study wishes to compare gut microbiota, host metabolic and gene expression in healthy, matched subjects to patients with liver disease of alcoholic and non-alcoholic etiology.

---

Rationale

We hypothesize that specific compositional and functional changes in the gut microbiota together with host metabolic and gene expression changes are key predictors for the development and progression of liver fibrosis, the precursor of cirrhosis, in alcohol overusing individuals and individuals with non-alcoholic fatty liver disease. To test the hypothesis, we need to compare changes in diseased individuals with a control cohort of healthy subjects.  

This project is part of the  GALAXY consortium (Gut-and-liver-axis in alcoholic liver fibrosis), which is exploring the role of the gut microbiome in alcoholic liver fibrosis to improve understanding, diagnosis, prevention and treatment of chronic liver disease. Additionally, the following projects are also a part of the GALAXY consortium:  OP_40 and  OP_80.

---

Description of the cohort

In GALA-HP we will establish a cross-sectional study at Odense University Hospital comprising 150 healthy individuals from the age 18-75, whom will be included over the next 24 months. 

Data and biological material

Pre-screening (duration: 5 min.)

• Online Questionnaire

First inclusion visit (duration: 2 hours)

• Weight and height
• Heart rate, blood pressure and EKG
• QoL and food frequency questionnaire (FFQ) and other baseline questions
• Nutritional status, hand-grip strength, abdominal circumference bio impedance
• Blood testing
• Tissue sampling for biobank (blood, urine, sputum, stool)
• Liver Stiffness measurement and abdominal ultrasound

Second inclusion visit (duration: 3-4 hours)

• Sigmoidoscopy + biopsies
• Magnetic resonance scan  

Collaborating researchers and departments

Department of Clinical Biochemistry and Pharmacology

• Associate Professor Sönke Detlefsen

Novo Nordisk Center for Basic Metabolic Research

• Professor Torben Hansen

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

• Postdoctoral fellow Shinichi Sunagawa

Academy of Athens, Greece

• Consultant Foteini Christodoulou  

NNF 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 

Publications associated with the project

Van Espen L, Bak EG, Beller L, Close L, Deboutte W, Juel HB, Nielsen T, Sinar D, De Coninck L, Frithioff-Bøjsøe C, Fonvig CE, Jacobsen S, Kjærgaard M, Thiele M, Fullam A, Kuhn M, Holm JC, Bork P, Krag A, Hansen T, Arumugam M, Matthijnssens J. A Previously Undescribed Highly Prevalent Phage Identified in a Danish Enteric Virome Catalog. mSystems. 2021 Oct 26;6(5):e0038221. doi: 10.1128/mSystems.00382-21. Epub 2021 Oct 19. PMID: 34665009; PMCID: PMC8525569.

Madsen, B. S., Thiele, M., Detlefsen, S., Kjaergaard, M., Møller, L. S., Trebicka, J., Nielsen, M. J., Gudmann, N. S., Leeming, D. J., Karsdal, M. A., & Krag, A. (2021). PRO-C3 and ADAPT algorithm accurately identify patients with advanced fibrosis due to alcohol-related liver disease. Alimentary Pharmacology & Therapeutics, 54(5), 699-708. https://doi.org/10.1111/apt.16513

Thiele M, Johansen S, Gudmann NS, Madsen B, Kjaergaard M, Nielsen MJ, Leeming DJ, Jacobsen S, Bendtsen F, Møller S, Detlefsen S, Karsdal M, Krag A; GALAXY Consortium. Progressive alcohol-related liver fibrosis is characterised by imbalanced collagen formation and degradation. Aliment Pharmacol Ther. 2021 Oct;54(8):1070-1080. doi: 10.1111/apt.16567. Epub 2021 Aug 24. PMID: 34428307.