• The carnitine-butyrobetaine-TMAO pathway after cardiac transplant: Impact on cardiac allograft vasculopathy and acute rejection 

      Trøseid, Marius; Mayerhofer, Christiane Caroline; Broch, Kaspar; Arora, Satish; Svardal, Asbjørn M.; Hov, Johannes Espolin Roksund; Andreassen, Arne K.; Gude, Einar; Karason, Kristjan; Dellgren, Gøran; Berge, Rolf Kristian; Gullestad, Lars; Aukrust, Pål; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-06-19)
      <p><i>BACKGROUND - </i>Alterations in the partly microbiota-dependent carnitine–γ-butyrobetaine (γBB)–trimethylamine N-oxide (TMAO) pathway have been linked to the progression of heart failure and atherosclerotic disease. We evaluated if circulating γBB, TMAO, and their common precursors carnitine and trimethyllysine (TML) were dysregulated after heart transplantation and associated with development ...
    • Design of the GutHeart—targeting gut microbiota to treat heart failure—trial: a Phase II, randomized clinical trial 

      Mayerhofer, Christiane Caroline; Awoyemi, Ayodeji Olawale; Moscavitch, Samuel D.; Lappegård, Knut Tore; Hov, Johannes Espolin Roksund; Aukrust, Pål; Hovland, Anders; Lorenzo, Andrea; Halvorsen, Sigrun; Seljeflot, Ingebjørg; Gullestad, Lars; Trøseid, Marius; Broch, Kaspar (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-08-07)
      <p><i>Aims</i>: Heart failure (HF) is a multifactorial disease. Current treatments target only a fraction of the putative pathophysiological pathways. In patients with HF, reduced cardiac output and congestion cause increased gut wall permeability. It has been suggested that leakage of microbial products is detrimental to the heart, at least partly through activation of systemic inflammatory pathways, ...
    • Detailed stratified GWAS analysis for severe COVID-19 in four European populations 

      Ellinghaus, David; Degenhardt, Frauke; Juzenas, Simonas; Lerga-Jaso, Jon; Wendorff, Mareike; Maya-Miles, Douglas; Uellendahl-Werth, Florian; ElAbd, Hesham; Lenning, Ole Bernt; Myhre, Ronny; Vadla, May Sissel; Holten, Aleksander Rygh; Kildal, Anders Benjamin; Lind, Andreas; Dyrhol-Riise, Anne Ma; Hoff, Dag Arne Lihaug; Müller, Fredrik; Solligård, Erik; Holter, Jan Cato; Afset, Jan Egil; Damås, Jan Kristian; Bergan, Jonas; Risnes, Kari; Muller, Karl Erik; Tonby, Kristian; Heggelund, Lars; Tuset Gustad, Trine; Grimsrud, Marit Mæhle; Dudman, Susanne Gjeruldsen; Folseraas, Trine; Skogen, Vegard; Hov, Johannes Espolin Roksund; Karlsen, Tom Hemming (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-15)
      Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from ...
    • Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19 

      Trøseid, Marius; Holter, Jan Cato; Holm, Kristian; Vestad, Beate; Sazonova, Taisiia; Granerud, Beathe Kiland; Dyrhol-Riise, Anne Ma; Holten, Aleksander Rygh; Tonby, Kristian; Kildal, Anders Benjamin; Heggelund, Lars; Tveita, Anders Aune; Bøe, Simen; Müller, Karl Erik; Jenum, Synne; Hov, Johannes Espolin Roksund; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-02-23)
      Background - Gut microbiota alterations have been reported in hospitalized COVID-19 patients, with reduced alpha diversity and altered microbiota composition related to respiratory failure. However, data regarding gut microbiota and mortality are scarce.<p> <p>Methods - Rectal swabs for gut microbiota analyses were collected within 48 h after hospital admission (baseline; n = 123) and three-month ...
    • Gut microbiota-dependent trimethylamine N-oxide associates with inflammation in common variable immunodeficiency 

      Macpherson, Magnhild Eide; Hov, Johannes Espolin Roksund; Ueland, Thor; Dahl, Tuva Børresdatter; Kummen, Martin; Otterdal, Kari; Holm, Kristian; Berge, Rolf Kristian; Mollnes, Tom Eirik; Trøseid, Marius; Halvorsen, Bente; Aukrust, Pål; Fevang, Børre; Jørgensen, Silje Fjellgård (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-16)
      A substantial proportion of patients with common variable immunodeficiency (CVID) have inflammatory and autoimmune complications of unknown etiology. We have previously shown that systemic inflammation in CVID correlates with their gut microbial dysbiosis. The gut microbiota dependent metabolite trimethylamine N-oxide (TMAO) has been linked to several metabolic and inflammatory disorders, but has ...
    • Increased secondary/primary bile acid ratio in chronic heart failure 

      Mayerhofer, Christiane Caroline; Ueland, Thor; Broch, Kaspar; Vincent, Royce P.; Cross, Gemma F.; Dahl, Christen Peder; Aukrust, Pål; Gullestad, Lars; Hov, Johannes Espolin Roksund; Trøseid, Marius (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-09-09)
      <p><i>Objective</i> Bile acids (BAs) are now recognized as signaling molecules and emerging evidence suggests that BAs affect cardiovascular function. The gut microbiota has recently been linked to the severity of heart failure (HF), and microbial metabolism has a major impact on BA homeostasis. We aimed to investigate the pattern of BAs, and particularly microbiota-transformed (secondary) BAs, in ...
    • Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure 

      Nendl, Andraz; Raju, Sajan; Broch, Kaspar; Mayerhofer, Christiane Caroline; Holm, Kristian; Halvorsen, Bente; Lappegård, Knut Tore; Moscavitch, Samuel; Hov, Johannes Espolin Roksund; Seljeflot, Ingebjørg; Trøseid, Marius; Awoyemi, Ayodeji Olawale (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-02)
      Background: The gut microbiota in patients with chronic heart failure (HF) is characterized by low bacterial diversity and reduced ability to synthesize beneficial metabolites. These changes may facilitate leakage of whole bacteria or bacterial products from the gut into the bloodstream, which may activate the innate immune system and contribute to the low-grade inflammation seen in HF. In this ...
    • Major increase in microbiota-dependent proatherogenic metabolite TMAO one year after bariatric surgery 

      Trøseid, Marius; Hov, Johannes Espolin Roksund; Nestvold, Torunn Kristin; Thoresen, Hanne; Berge, Rolf Kristian; Svardal, Asbjørn M.; Lappegård, Knut Tore (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-04-15)
      Background: Trimethylamine-N-oxide (TMAO) is formed in the liver from trimethylamine (TMA), a product exclusively generated by the gut microbiota from dietary phosphatidylcholine and carnitine. An alternative pathway of TMAO formation from carnitine is via the microbiota-dependent intermediate g-butyrobetaine (gBB). Elevated TMAO levels are associated with cardiovascular disease (CVD), but little ...
    • Mapping the human genetic architecture of COVID-19 

      Niemi, Mari E.K.; Karjalainen, Juha; Liao, Rachel G.; Neale, Benjamin M.; Daly, Mark; Ganna, Andrea; Pathak, Gita A.; Andrews, Shea J.; Kanai, Masahiro; Veerapen, Kumar; Fernandez-Cadenas, Israel; Schulte, Eva C.; Striano, Pasquale; Afset, Jan Egil; Solligård, Erik; Damås, Jan Kristian; Risnes, Kari; Bettini, Laura Rachele; Gustad, Lise Tuset; Holter, Jan Cato; Hov, Johannes Espolin Roksund; Karlsen, Tom Hemming; Folseraas, Trine; Holten, Aleksander Rygh; Dyrhol-Riise, Anne Ma; Tonby, Kristian; Lind, Andreas; Müller, Fredrik; Dudman, Susanne Gjeruldsen; Grimsrud, Marit Mæhle; Vadla, May Sissel; Myhre, Ronny; Kildal, Anders Benjamin; Hoff, Dag Arne Lihaug; Muller, Karl Erik; Heggelund, Lars; Bergan, Jonas; Skogen, Vegard (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-08)
      The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal ...
    • Reduced gut microbial diversity in familial hypercholesterolemia with no effect of omega-3 polyunsaturated fatty acids intervention–a pilot trial 

      Larsen, Christopher Storm; Hande, Liv Nesse; Kummen, Martin; Thunhaug, Hilde; Vestad, Beate; Hansen, Simen Hyll; Hovland, Anders Wilhelm; Trøseid, Marius; Lappegård, Knut Tore; Hov, Johannes Espolin Roksund (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-08-01)
      Individuals with familial hypercholesterolemia (FH) undergo an aggressive treatment with cholesterollowering drugs to prevent coronary heart disease. Recent evidence suggests an interplay between the gut microbiota, blood lipid levels and lipid-lowering drugs, but this has yet to be studied in individuals with FH. The objective of the study was to characterize the gut microbiota of individuals ...
    • Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency 

      Jørgensen, Silje Fjellgård; Macpherson, Magnhild Eide; Bjørnetrø, Tonje; Holm, Kristian; Kummen, Martin; Rashidi, Azita; Michelsen, Annika; Lekva, Tove; Halvorsen, Bente; Trøseid, Marius; Mollnes, Tom Eirik; Berge, Rolf Kristian; Yndestad, Arne; Ueland, Thor; Karlsen, Tom Hemming; Aukrust, Pål; Hov, Johannes Espolin Roksund; Fevang, Børre (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-01-17)
      Common variable immunodeficiency (CVID) patients have reduced gut microbial diversity compared to healthy controls. The reduced diversity is associated with gut leakage, increased systemic inflammation and ten “key” bacteria that capture the gut dysbiosis (dysbiosis index) in CVID. Rifaximin is a broad-spectrum non-absorbable antibiotic known to reduce gut leakage (lipopolysaccharides, LPS) in liver ...
    • Rifaximin or Saccharomyces boulardii in heart failure with reduced ejection fraction: Results from the randomized GutHeart trial 

      Awoyemi, Ayodeji Olawale; Mayerhofer, Cristiane; Felix, Alex S.; Hov, Johannes Espolin Roksund; Moscavitch, Samuel D.; Lappegård, Knut Tore; Hovland, Anders; Halvorsen, Sigrun; Halvorsen, Bente; Gregersen, Ida; Svardal, Asbjørn M.; Berge, Rolf Kristian; Hansen, Simen Hyll; Götz, Alexandra; Holm, Kristian; Aukrust, Pål; Åkra, Sissel; Seljeflot, Ingebjørg; Solheim, Svein; Lorenzo, Andrea; Gullestad, Lars; Trøseid, Marius; Broch, Kaspar (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-28)
      Background - The gut microbiota represents a potential treatment target in heart failure (HF) through microbial metabolites such as trimethylamine N-oxide (TMAO) and systemic inflammation. Treatment with the probiotic yeast Saccharomyces boulardii have been suggested to improve left ventricular ejection fraction (LVEF).<p> <p>Methods - In a multicentre, prospective randomized open label, blinded ...
    • Rosuvastatin alters the genetic composition of the human gut microbiome 

      Kummen, Martin; Solberg, Ole Geir; Larsen, Christopher Storm; Holm, Kristian; Ragnarsson, Asgrimur; Trøseid, Marius; Vestad, Beate; Skårdal, Rita; Yndestad, Arne; Ueland, Thor; Svardal, Asbjørn M.; Berge, Rolf Kristian; Seljeflot, Ingebjørg; Gullestad, Lars; Karlsen, Tom Hemming; Aaberge, Lars; Aukrust, Pål; Hov, Johannes Espolin Roksund (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-03-25)
      The gut microbiome contributes to the variation of blood lipid levels, and secondary bile acids are associated with the effect of statins. Yet, our knowledge of how statins, one of our most common drug groups, affect the human microbiome is scarce. We aimed to characterize the effect of rosuvastatin on gut microbiome composition and inferred genetic content in stool samples from a randomized controlled ...
    • SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells 

      Hammer, Quirin; Dunst, Josefine; Christ, Wanda; Picarazzi, Francesca; Wendorff, Mareike; Momayyezi, Pouria; Huhn, Oisín; Netskar, Herman Krogstad; Maleki, Kimia T.; García, Marina; Sekine, Takuya; Sohlberg, Ebba; Azzimato, Valerio; Aouadi, Myriam; Holten, Aleksander Rygh; Kildal, Anders Benjamin; Lind, Andreas; Dyrhol-Riise, Anne Ma; Hoff, Dag Arne Lihaug; Solligård, Erik; Holter, Jan Cato; Afset, Jan Egil; Damås, Jan Kristian; Hov, Johannes Espolin Roksund; Bergan, Jonas; Risnes, Kari; Muller, Karl Erik; Tonby, Kristian; Heggelund, Lars; Gustad, Lise Tuset; Grimsrud, Marit Mæhle; Vadla, May Sissel; Lenning, Ole Bernt; Myhre, Ronny; Haider, Sammra; Dudman, Susanne Gjeruldsen; Karlsen, Tom Hemming; Folseraas, Trine; Skogen, Vegard; Degenhardt, Frauke; Franke, Andre; Spallotta, Francesco; Mori, Mattia; Michaëlsson, Jakob; Björkström, Niklas K.; Rückert, Timo; Romagnani, Chiara; Horowitz, Amir; Klingström, Jonas; Ljunggren, Hans-Gustaf; Malmberg, Karl-Johan (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-02-21)
      Natural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown. Here, we show that the ...