Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure

BackgroundThe 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 act...

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Main Authors: Andraž Nendl, Sajan C. Raju, Kaspar Broch, Cristiane C. K. Mayerhofer, Kristian Holm, Bente Halvorsen, Knut Tore Lappegård, Samuel Moscavitch, Johannes Roksund Hov, Ingebjørg Seljeflot, Marius Trøseid, Ayodeji Awoyemi
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Cardiovascular Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1160030/full
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author Andraž Nendl
Andraž Nendl
Sajan C. Raju
Kaspar Broch
Cristiane C. K. Mayerhofer
Kristian Holm
Kristian Holm
Kristian Holm
Bente Halvorsen
Bente Halvorsen
Knut Tore Lappegård
Knut Tore Lappegård
Samuel Moscavitch
Johannes Roksund Hov
Johannes Roksund Hov
Johannes Roksund Hov
Johannes Roksund Hov
Ingebjørg Seljeflot
Ingebjørg Seljeflot
Ingebjørg Seljeflot
Marius Trøseid
Marius Trøseid
Ayodeji Awoyemi
Ayodeji Awoyemi
author_facet Andraž Nendl
Andraž Nendl
Sajan C. Raju
Kaspar Broch
Cristiane C. K. Mayerhofer
Kristian Holm
Kristian Holm
Kristian Holm
Bente Halvorsen
Bente Halvorsen
Knut Tore Lappegård
Knut Tore Lappegård
Samuel Moscavitch
Johannes Roksund Hov
Johannes Roksund Hov
Johannes Roksund Hov
Johannes Roksund Hov
Ingebjørg Seljeflot
Ingebjørg Seljeflot
Ingebjørg Seljeflot
Marius Trøseid
Marius Trøseid
Ayodeji Awoyemi
Ayodeji Awoyemi
author_sort Andraž Nendl
collection DOAJ
description BackgroundThe 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 exploratory cross-sectional study, we aimed to investigate relationships between gut microbiota diversity, markers of gut barrier dysfunction, inflammatory markers, and cardiac function in chronic HF patients.MethodsIn total, 151 adult patients with stable HF and left ventricular ejection fraction (LVEF) < 40% were enrolled. We measured lipopolysaccharide (LPS), LPS-binding protein (LBP), intestinal fatty acid binding protein (I-FABP), and soluble cluster of differentiation 14 (sCD14) as markers of gut barrier dysfunction. N-terminal pro-B-type natriuretic peptide (NT-proBNP) level above median was used as a marker of severe HF. LVEF was measured by 2D-echocardiography. Stool samples were sequenced using 16S ribosomal RNA gene amplification. Shannon diversity index was used as a measure of microbiota diversity.ResultsPatients with severe HF (NT-proBNP > 895 pg/ml) had increased I-FABP (p < 0.001) and LBP (p = 0.03) levels. ROC analysis for I-FABP yielded an AUC of 0.70 (95% CI 0.61–0.79, p < 0.001) for predicting severe HF. A multivariate logistic regression model showed increasing I-FABP levels across quartiles of NT-proBNP (OR 2.09, 95% CI 1.28−3.41, p = 0.003). I-FABP was negatively correlated with Shannon diversity index (rho = −0.30, p = <0.001), and the bacterial genera Ruminococcus gauvreauii group, Bifidobacterium, Clostridium sensu stricto, and Parasutterella, which were depleted in patients with severe HF.ConclusionsIn patients with HF, I-FABP, a marker of enterocyte damage, is associated with HF severity and low microbial diversity as part of an altered gut microbiota composition. I-FABP may reflect dysbiosis and may be a marker of gut involvement in patients with HF.
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spelling doaj.art-8d10a313240f47f88c7a5c2ddbedbcfc2023-06-02T05:51:55ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-06-011010.3389/fcvm.2023.11600301160030Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failureAndraž Nendl0Andraž Nendl1Sajan C. Raju2Kaspar Broch3Cristiane C. K. Mayerhofer4Kristian Holm5Kristian Holm6Kristian Holm7Bente Halvorsen8Bente Halvorsen9Knut Tore Lappegård10Knut Tore Lappegård11Samuel Moscavitch12Johannes Roksund Hov13Johannes Roksund Hov14Johannes Roksund Hov15Johannes Roksund Hov16Ingebjørg Seljeflot17Ingebjørg Seljeflot18Ingebjørg Seljeflot19Marius Trøseid20Marius Trøseid21Ayodeji Awoyemi22Ayodeji Awoyemi23Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayDepartment of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, NorwayDepartment of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayNorwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayDivision of Internal Medicine, Nordland Hospital, Bodø, NorwayInstitute of Clinical Medicine, University of Tromsø, Tromsø, NorwayLaboratory of Immunopharmacology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, BrazilInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, NorwayNorwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, NorwaySection of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, Norway0Department of Cardiology, Oslo University Hospital Ullevål, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, Norway1Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway0Department of Cardiology, Oslo University Hospital Ullevål, Oslo, NorwayBackgroundThe 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 exploratory cross-sectional study, we aimed to investigate relationships between gut microbiota diversity, markers of gut barrier dysfunction, inflammatory markers, and cardiac function in chronic HF patients.MethodsIn total, 151 adult patients with stable HF and left ventricular ejection fraction (LVEF) < 40% were enrolled. We measured lipopolysaccharide (LPS), LPS-binding protein (LBP), intestinal fatty acid binding protein (I-FABP), and soluble cluster of differentiation 14 (sCD14) as markers of gut barrier dysfunction. N-terminal pro-B-type natriuretic peptide (NT-proBNP) level above median was used as a marker of severe HF. LVEF was measured by 2D-echocardiography. Stool samples were sequenced using 16S ribosomal RNA gene amplification. Shannon diversity index was used as a measure of microbiota diversity.ResultsPatients with severe HF (NT-proBNP > 895 pg/ml) had increased I-FABP (p < 0.001) and LBP (p = 0.03) levels. ROC analysis for I-FABP yielded an AUC of 0.70 (95% CI 0.61–0.79, p < 0.001) for predicting severe HF. A multivariate logistic regression model showed increasing I-FABP levels across quartiles of NT-proBNP (OR 2.09, 95% CI 1.28−3.41, p = 0.003). I-FABP was negatively correlated with Shannon diversity index (rho = −0.30, p = <0.001), and the bacterial genera Ruminococcus gauvreauii group, Bifidobacterium, Clostridium sensu stricto, and Parasutterella, which were depleted in patients with severe HF.ConclusionsIn patients with HF, I-FABP, a marker of enterocyte damage, is associated with HF severity and low microbial diversity as part of an altered gut microbiota composition. I-FABP may reflect dysbiosis and may be a marker of gut involvement in patients with HF.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1160030/fullheart failuregut leakagegut microbiotaintestinal fatty acid binding protein (I-FABP)dysbiosis
spellingShingle Andraž Nendl
Andraž Nendl
Sajan C. Raju
Kaspar Broch
Cristiane C. K. Mayerhofer
Kristian Holm
Kristian Holm
Kristian Holm
Bente Halvorsen
Bente Halvorsen
Knut Tore Lappegård
Knut Tore Lappegård
Samuel Moscavitch
Johannes Roksund Hov
Johannes Roksund Hov
Johannes Roksund Hov
Johannes Roksund Hov
Ingebjørg Seljeflot
Ingebjørg Seljeflot
Ingebjørg Seljeflot
Marius Trøseid
Marius Trøseid
Ayodeji Awoyemi
Ayodeji Awoyemi
Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure
Frontiers in Cardiovascular Medicine
heart failure
gut leakage
gut microbiota
intestinal fatty acid binding protein (I-FABP)
dysbiosis
title Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure
title_full Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure
title_fullStr Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure
title_full_unstemmed Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure
title_short Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure
title_sort intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure
topic heart failure
gut leakage
gut microbiota
intestinal fatty acid binding protein (I-FABP)
dysbiosis
url https://www.frontiersin.org/articles/10.3389/fcvm.2023.1160030/full
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