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Genomics and Metagenomics in Inflammatory Disorders

The projects in the Genomics and Metagenomics Group aim to characterize and understand how alterations in the human genome and the gut microbial flora influence primary sclerosing cholangitis (PSC) susceptibility and cholangiocarcinoma development. We do this by applying modern genotyping and sequencing technologies in cross-sectional and interventional study designs.

About the group

Genetic factors are likely to play an important role in PSC development, as shown by an increased risk of disease in first degree relatives of patients with PSC. By studying disease genes and their function, the mechanisms by which PSC develop and eventually may be treated can be defined. Since many of the patients with PSC have concurrent inflammatory diseases (mainly inflammatory bowel disease, but also prototypical autoimmune diseases like type 1 diabetes and rheumatoid arthritis), these diseases are studied in parallel.

The gut microbiota is an important human organ comprising more cells than the body itself, and likely plays a major role in human disease. Ongoing studies aim to characterize how the gut microbial community composition in patients with PSC interacts with immune regulation, bile acid metabolism and drugs.  An important part of the activities is the standardization of methods related to key challenges in the field; study designs, sample collection and preparation, sequencing technology and bioinformatics.

Lifetime risk of cancer of the bile ducts in patients with PSC is 10-20%. Few inflammatory conditions have an equally high risk of cancer development, and determining the genetic and epigenetic alterations responsible for this is of great importance. In addition to understanding the pathogenesis of cholangiocarcinoma, cancer genetics and epigenetics may serve as diagnostic and prognostic markers.

Collaborators

  • Andre Franke, Institute of Clinical Molecular Biology, Christian Albrecht's University, Kiel, Germany
  • Fredrik Bäckhed and Hanns-Ulrich Marschall, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden
  • Karsen Kristiansen (University of Copenhagen) and Susanne Brix (Denmark's Technical University), Copenhagen, Denmark

Selected Publications

  • Alberts R, de Vries EMG, Goode EC, Jiang X, Sampaziotis F, Rombouts K, Böttcher K, Folseraas T, Weismüller TJ, Mason AL, Wang W, Alexander G, Alvaro D, Bergquist A, Björkström NK, Beuers U, Björnsson E, Boberg KM, Bowlus CL, Bragazzi MC, Carbone M, Chazouillères O, Cheung A, Dalekos G, Eaton J et al. (2017) Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis. Gut (in press)
  • de Muinck EJ, Trosvik P, Gilfillan GD, Hov JR, Sundaram AYM (2017) A novel ultra high-throughput 16S rRNA gene amplicon sequencing library preparation method for the Illumina HiSeq platform Microbiome, 5 (1), 68
  • de Vries EMG, Färkkilä M, Milkiewicz P, Hov JR, Eksteen B, Thorburn D, Chazouillères O, Pares A, Nygård S, Gilja OH, Wunsch E, Invernizzi P, Carbone M, Bernuzzi F, Boberg KM, Røsjø H, Rosenberg W, Beuers UH, Ponsioen CY, Karlsen TH, Vesterhus M (2017) Enhanced liver fibrosis test predicts transplant-free survival in primary sclerosing cholangitis, a multi-centre study Liver Int, 37 (10), 1554-1561
  • Haissman JM, Haugaard AK, Ostrowski SR, Berge RK, Hov JR, Trøseid M, Nielsen SD (2017) Microbiota-dependent metabolite and cardiovascular disease marker trimethylamine-N-oxide (TMAO) is associated with monocyte activation but not platelet function in untreated HIV infection BMC Infect Dis, 17 (1), 445
  • Henriksen EKK, Viken MK, Wittig M, Holm K, Folseraas T, Mucha S, Melum E, Hov JR, Lazaridis KN, Juran BD, Chazouillères O, Färkkilä M, Gotthardt DN, Invernizzi P, Carbone M, Hirschfield GM, Rushbrook SM, Goode E, UK-PSC Consortium, Ponsioen CY, Weersma RK, Eksteen B, Yimam KK, Gordon SC, Goldberg D et al. (2017) HLA haplotypes in primary sclerosing cholangitis patients of admixed and non-European ancestry HLA, 90 (4), 228-233
  • Hov JR, Karlsen TH (2017) The Microbiome in Primary Sclerosing Cholangitis: Current Evidence and Potential Concepts Semin Liver Dis, 37 (4), 314-331
  • Hov JR, Kummen M (2017) Intestinal microbiota in primary sclerosing cholangitis Curr Opin Gastroenterol, 33 (2), 85-92
  • Jahnsen FL, Bækkevold ES, Hov JR, Landsverk OJ (2017) Do Long-Lived Plasma Cells Maintain a Healthy Microbiota in the Gut? Trends Immunol (in press)
  • Koch M, Freitag-Wolf S, Schlesinger S, Borggrefe J, Hov JR, Jensen MK, Pick J, Markus MRP, Höpfner T, Jacobs G, Siegert S, Artati A, Kastenmüller G, Römisch-Margl W, Adamski J, Illig T, Nothnagel M, Karlsen TH, Schreiber S, Franke A, Krawczak M, Nöthlings U, Lieb W (2017) Serum metabolomic profiling highlights pathways associated with liver fat content in a general population sample Eur J Clin Nutr, 71 (8), 995-1001
  • Lunder AK, Jahnsen J, Bakstad LT, Borthne A, Hov JR, Vatn M, Negård A, IBSEN Study Group (2017) Bowel Damage in Patients With Long-term Crohn's Disease, Assessed by Magnetic Resonance Enterography and the Lémann Index Clin Gastroenterol Hepatol, 16 (1), 75-82.e5
  • Mayerhofer CCK, Ueland T, Broch K, Vincent RP, Cross GF, Dahl CP, Aukrust P, Gullestad L, Hov JR, Trøseid M (2017) Increased Secondary/Primary Bile Acid Ratio in Chronic Heart Failure J Card Fail, 23 (9), 666-671
  • Rühlemann MC, Degenhardt F, Thingholm LB, Wang J, Skiecevičienė J, Rausch P, Hov JR, Lieb W, Karlsen TH, Laudes M, Baines JF, Heinsen FA, Franke A (2017) Application of the distance-based F test in an mGWAS investigating β diversity of intestinal microbiota identifies variants in SLC9A8 (NHE8) and 3 other loci Gut Microbes, 1-8 (in press)
  • Tronstad RR, Kummen M, Holm K, von Volkmann HL, Anmarkrud JA, Høivik ML, Moum B, Gilja OH, Hausken T, Baines J, Karlsen TH, Fiskerstrand T, Hov JR (2017) Guanylate Cyclase C Activation Shapes the Intestinal Microbiota in Patients with Familial Diarrhea and Increased Susceptibility for Crohn's Disease Inflamm Bowel Dis, 23 (10), 1752-1761
  • Vesterhus M, Holm A, Hov JR, Nygård S, Schrumpf E, Melum E, Thorbjørnsen LW, Paulsen V, Lundin K, Dale I, Gilja OH, Zweers SJLB, Vatn M, Schaap FG, Jansen PLM, Ueland T, Røsjø H, Moum B, Ponsioen CY, Boberg KM, Färkkilä M, Karlsen TH, Lund-Johansen F (2017) Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis J Hepatol, 66 (6), 1214-1222
  • Volkmann ER, Hoffmann-Vold AM, Chang YL, Jacobs JP, Tillisch K, Mayer EA, Clements PJ, Hov JR, Kummen M, Midtvedt Ø, Lagishetty V, Chang L, Labus JS, Molberg Ø, Braun J (2017) Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts BMJ Open Gastroenterol, 4 (1), e000134
Published Feb. 4, 2014 3:37 PM - Last modified Sep. 19, 2019 1:49 PM

Contact

Group leader

Johannes Roksund Hov