About the group
The research group is studying the influence of the gut microbiome on inflammatory diseases, with a particular emphasis on the liver disease primary sclerosing cholangitis (PSC) and on inflammatory bowel disease (IBD), which is associated with PSC.
We use genetic and metabolomic methods, and cross-sectional, longitudinal and interventional designs.
We also investigate the gut microbiota experimentally in animal models. The main aims are to identify causes of diseases and to establish microbiota medicine as a clinical field with an emphasis on biomarkers and therapy.
Ongoing research activity
The overall research agenda and strategies are well-defined with a balance between the major focus on the liver disease primary sclerosing cholangitis (PSC) and associated conditions, and a more general focus on the strategic research area Personalized treatment in clinical microbiota medicine.
The first step of our translational research program is to characterize in detail microbiome in the disease by using metagenomic (sequencing-based) and metabolomic methodology. We study this in detail in PSC as well as recurrent PSC after liver transplantation, and the closely associated inflammatory bowel diseases. As part of the ERC Starting Grant project StopAutoimmunity, we use recurrent PSC as disease model, and we recently identified overlapping features of the mucosal microbiota composition before and after liver transplantation. This provides a strong rationale for further search for markers of microbial functions in PSC and rPSC. In ongoing work we therefore perform unbiased screening for alterations of microbial metabolites in blood. Similar strategies have been or are being employed in other disease states that we have examined during the past decade, including inflammatory bowel diseases, immunodeficiencies, and heart failure.
In the next steps, clinical relevance is established by investigations of altered microbial functions as biomarkers. We now follow up on several interesting findings, including new data on the importance of e.g. vitamin B6. In parallel, we now work extensively with experimental animal models in germ-free, gnotobiotic or conventional setting to investigate cause and effect of microbial alterations observed in PSC. This is crucial to establish a rationale for e.g. therapeutic trials. Clinical “proof-of-concept” trials are needed to establish feasibility and mechanistic evidence of a role of the gut microbiome and our first clinical trial in PSC based on our own observations (vit B6 supplementation) will soon be initiated. Clinical trials targeting the gut are also important in our Strategic research area.
Notably, the group activities also try to answer other questions, including autoimmunity in PSC, molecular mechanisms of PSC and rPSC, including modern methods of spatial and tissue transcriptomics, molecular aspects of the GPR35, with clinical translation as important goals.
Selected Publications
- Role of microbiome in autoimmune liver diseases. Schneider KM, Kummen M, Trivedi PJ, Hov JR. Hepatology. 2023 Jun 27. doi: 10.1097/HEP.0000000000000506. Online ahead of print. PMID: 37369002
- Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation. Braadland PR, Bergquist A, Kummen M, Bossen L, Engesæter LK, Reims HM, Björk I, Grzyb K, Abildgaard A, Småstuen MC, Folseraas T, Trøseid M, Ulvik A, Ueland PM, Melum E, Line PD, Høivik ML, Grønbæk H, Karlsen TH, Vesterhus M, Hov JR. J Hepatol. 2023 Oct;79(4):955-966. doi: 10.1016/j.jhep.2023.05.038. Epub 2023 Jun 14. PMID: 37328069
- The microbiota and the gut-liver axis in primary sclerosing cholangitis. Hov JR, Karlsen TH. Nat Rev Gastroenterol Hepatol. 2023 Mar;20(3):135-154. doi: 10.1038/s41575-022-00690-y. Epub 2022 Nov 9. PMID: 36352157 Review.
- Suppression of bile acid synthesis as a tipping point in the disease course of primary sclerosing cholangitis. Braadland PR, Schneider KM, Bergquist A, Molinaro A, Lövgren-Sandblom A, Henricsson M, Karlsen TH, Vesterhus M, Trautwein C, Hov JR, Marschall HU. JHEP Rep. 2022 Aug 18;4(11):100561. doi: 10.1016/j.jhepr.2022.100561. eCollection 2022 Nov. PMID: 36176935 Free PMC article.
- A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation. Hole MJ, Jørgensen KK, Holm K, Braadland PR, Meyer-Myklestad MH, Medhus AW, Reikvam DH, Götz A, Grzyb K, Boberg KM, Karlsen TH, Kummen M, Hov JR. Hepatology. 2023 Mar 1;77(3):715-728. doi: 10.1002/hep.32773. Epub 2023 Feb 17. PMID: 36056902 Free PMC article.
- Altered Gut Microbial Metabolism of Essential Nutrients in Primary Sclerosing Cholangitis. Kummen M, Thingholm LB, Rühlemann MC, Holm K, Hansen SH, Moitinho-Silva L, Liwinski T, Zenouzi R, Storm-Larsen C, Midttun Ø, McCann A, Ueland PM, Høivik ML, Vesterhus M, Trøseid M, Laudes M, Lieb W, Karlsen TH, Bang C, Schramm C, Franke A, Hov JR. Gastroenterology. 2021 Apr;160(5):1784-1798.e0. doi: 10.1053/j.gastro.2020.12.058. Epub 2020 Dec 31. PMID: 33387530 Free PMC article.
- Rosuvastatin alters the genetic composition of the human gut microbiome. Kummen M, Solberg OG, Storm-Larsen C, Holm K, Ragnarsson A, Trøseid M, Vestad B, Skårdal R, Yndestad A, Ueland T, Svardal A, Berge RK, Seljeflot I, Gullestad L, Karlsen TH, Aaberge L, Aukrust P, Hov JR. Sci Rep. 2020 Mar 25;10(1):5397. doi: 10.1038/s41598-020-62261-y. PMID: 32214138 Free PMC article. Clinical Trial.
- Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis. Jendrek ST, Gotthardt D, Nitzsche T, Widmann L, Korf T, Michaels MA, Weiss KH, Liaskou E, Vesterhus M, Karlsen TH, Mindorf S, Schemmer P, Bär F, Teegen B, Schröder T, Ehlers M, Hammers CM, Komorowski L, Lehnert H, Fellermann K, Derer S, Hov JR, Sina C. Gut. 2017 Jan;66(1):137-144. doi: 10.1136/gutjnl-2016-311739. Epub 2016 Jul 12. PMID: 27406039
- Prevalence of Sclerosing Cholangitis Detected by Magnetic Resonance Cholangiography in Patients With Long-term Inflammatory Bowel Disease. Lunder AK, Hov JR, Borthne A, Gleditsch J, Johannesen G, Tveit K, Viktil E, Henriksen M, Hovde Ø, Huppertz-Hauss G, Høie O, Høivik ML, Monstad I, Solberg IC, Jahnsen J, Karlsen TH, Moum B, Vatn M, Negård A. Gastroenterology. 2016 Oct;151(4):660-669.e4. doi: 10.1053/j.gastro.2016.06.021. Epub 2016 Jun 21. PMID: 27342213
- The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls. Kummen M, Holm K, Anmarkrud JA, Nygård S, Vesterhus M, Høivik ML, Trøseid M, Marschall HU, Schrumpf E, Moum B, Røsjø H, Aukrust P, Karlsen TH, Hov JR. Gut. 2017 Apr;66(4):611-619. doi: 10.1136/gutjnl-2015-310500. Epub 2016 Feb 17. PMID: 26887816
- The gut microbiota contributes to a mouse model of spontaneous bile duct inflammation. Schrumpf E, Kummen M, Valestrand L, Greiner TU, Holm K, Arulampalam V, Reims HM, Baines J, Bäckhed F, Karlsen TH, Blumberg RS, Hov JR, Melum E. J Hepatol. 2017 Feb;66(2):382-389. doi: 10.1016/j.jhep.2016.09.020. Epub 2016 Oct 5. PMID: 27720803 Free PMC article.
- Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation. Jørgensen SF, Trøseid M, Kummen M, Anmarkrud JA, Michelsen AE, Osnes LT, Holm K, Høivik ML, Rashidi A, Dahl CP, Vesterhus M, Halvorsen B, Mollnes TE, Berge RK, Moum B, Lundin KE, Fevang B, Ueland T, Karlsen TH, Aukrust P, Hov JR. Mucosal Immunol. 2016 Nov;9(6):1455-1465. doi: 10.1038/mi.2016.18. Epub 2016 Mar 16. PMID: 26982597
- Enhanced liver fibrosis score predicts transplant-free survival in primary sclerosing cholangitis. Vesterhus M, Hov JR, Holm A, Schrumpf E, Nygård S, Godang K, Andersen IM, Naess S, Thorburn D, Saffioti F, Vatn M, Gilja OH, Lund-Johansen F, Syversveen T, Brabrand K, Parés A, Ponsioen CY, Pinzani M, Färkkilä M, Moum B, Ueland T, Røsjø H, Rosenberg W, Boberg KM, Karlsen TH. Hepatology. 2015 Jul;62(1):188-97. doi: 10.1002/hep.27825. Epub 2015 Apr 28. PMID: 25833813
- Association Between HLA Haplotypes and Increased Serum Levels of IgG4 in Patients With Primary Sclerosing Cholangitis. Berntsen NL, Klingenberg O, Juran BD, Benito de Valle M, Lindkvist B, Lazaridis KN, Boberg KM, Karlsen TH, Hov JR. Gastroenterology. 2015 May;148(5):924-927.e2. doi: 10.1053/j.gastro.2015.01.041. Epub 2015 Feb 2. PMID: 25655558 Free PMC article.
- Effects of coffee consumption, smoking, and hormones on risk for primary sclerosing cholangitis. Andersen IM, Tengesdal G, Lie BA, Boberg KM, Karlsen TH, Hov JR. Clin Gastroenterol Hepatol. 2014 Jun;12(6):1019-28. doi: 10.1016/j.cgh.2013.09.024. Epub 2013 Sep 25. PMID: 24076415
- Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Liu JZ, Hov JR, Folseraas T, Ellinghaus E, Rushbrook SM, Doncheva NT, Andreassen OA, Weersma RK, Weismüller TJ, Eksteen B, Invernizzi P, Hirschfield GM, Gotthardt DN, Pares A, Ellinghaus D, Shah T, Juran BD, Milkiewicz P, Rust C, Schramm C, Müller T, Srivastava B, Dalekos G, Nöthen MM, Herms S, Winkelmann J, Mitrovic M, Braun F, Ponsioen CY, Croucher PJ, Sterneck M, Teufel A, Mason AL, Saarela J, Leppa V, Dorfman R, Alvaro D, Floreani A, Onengut-Gumuscu S, Rich SS, Thompson WK, Schork AJ, Næss S, Thomsen I, Mayr G, König IR, Hveem K, Cleynen I, Gutierrez-Achury J, Ricaño-Ponce I, van Heel D, Björnsson E, Sandford RN, Durie PR, Melum E, Vatn MH, Silverberg MS, Duerr RH, Padyukov L, Brand S, Sans M, Annese V, Achkar JP, Boberg KM, Marschall HU, Chazouillères O, Bowlus CL, Wijmenga C, Schrumpf E, Vermeire S, Albrecht M; UK-PSCSC Consortium; Rioux JD, Alexander G, Bergquist A, Cho J, Schreiber S, Manns MP, Färkkilä M, Dale AM, Chapman RW, Lazaridis KN; International PSC Study Group; Franke A, Anderson CA, Karlsen TH; International IBD Genetics Consortium. Nat Genet. 2013 Jun;45(6):670-5. doi: 10.1038/ng.2616. Epub 2013 Apr 21. PMID: 23603763 Free PMC article.