Gut Dysbiosis in Patients With Fontan Circulation

Background The process underlying Fontan pathophysiology is multifactorial and may include gut dysbiosis (GD). We investigated the presence of GD and elucidated its correlation with Fontan pathophysiology. Methods and Results Gut microbiomes of 155 consecutive patients with Fontan pathophysiology an...

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Main Authors: Hideo Ohuchi, Ryotaro Asano, Aki Mori, Tomohiko Ishibashi, Daisuke Motooka, Michikazu Nakai, Yoshikazu Nakaoka
Format: Article
Language:English
Published: Wiley 2024-09-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.034538
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author Hideo Ohuchi
Ryotaro Asano
Aki Mori
Tomohiko Ishibashi
Daisuke Motooka
Michikazu Nakai
Yoshikazu Nakaoka
author_facet Hideo Ohuchi
Ryotaro Asano
Aki Mori
Tomohiko Ishibashi
Daisuke Motooka
Michikazu Nakai
Yoshikazu Nakaoka
author_sort Hideo Ohuchi
collection DOAJ
description Background The process underlying Fontan pathophysiology is multifactorial and may include gut dysbiosis (GD). We investigated the presence of GD and elucidated its correlation with Fontan pathophysiology. Methods and Results Gut microbiomes of 155 consecutive patients with Fontan pathophysiology and 44 healthy individuals were analyzed using 16S rRNA sequencing of bacterial DNA extracted from fecal samples. GD was evaluated on the basis of α and ß diversities of the gut microbiome and was compared with natural log‐transformed C‐reactive protein, hemodynamics, von Willebrand factor antigen (a bacterial translocation marker), Mac‐2 binding protein glycosylation isomer (a liver fibrosis indicator), peak oxygen uptake, and heart failure hospitalization. Patients with Fontan exhibited GD in terms of α and ß diversities as compared with controls (P<0.01). Reduced α diversity was associated with a failed hemodynamic phenotype, hypoxia, high natural log‐transformed C‐reactive protein levels, and elevated von Willebrand factor antigen and Mac‐2 binding protein glycosylation isomer levels (P<0.05–0.01). In addition to elevated von Willebrand factor antigen and hypoxia, decreased α diversity was independently correlated with a high natural log‐transformed C‐reactive protein level (P<0.05), which was associated with liver imaging abnormalities and a heightened risk of heart failure hospitalization (P<0.01 for both). Conclusions Patients with Fontan pathophysiology exhibited GD compared with healthy individuals, and GD was linked to failed hemodynamics and systemic inflammation with a poor prognosis. Therefore, GD may play a pivotal role in a failing Fontan status, including Fontan‐associated liver disease, through GD‐associated systemic inflammation.
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spelling doaj-art-efddf34032824bc09511cf7bc38cf4392025-08-20T01:52:53ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-09-01131810.1161/JAHA.124.034538Gut Dysbiosis in Patients With Fontan CirculationHideo Ohuchi0Ryotaro Asano1Aki Mori2Tomohiko Ishibashi3Daisuke Motooka4Michikazu Nakai5Yoshikazu Nakaoka6Department of Pediatric Cardiology National Cerebral and Cardiovascular Center Suita JapanDepartment of Vascular Physiology National Cerebral and Cardiovascular Center Research Institute Suita JapanDepartment of Pediatric Cardiology National Cerebral and Cardiovascular Center Suita JapanDepartment of Vascular Physiology National Cerebral and Cardiovascular Center Research Institute Suita JapanDepartment of Infection Metagenomics, Research Institute for Microbial Diseases Osaka University Suita JapanClinical Research Support Center University of Miyazaki Hospital Miyazaki JapanDepartment of Vascular Physiology National Cerebral and Cardiovascular Center Research Institute Suita JapanBackground The process underlying Fontan pathophysiology is multifactorial and may include gut dysbiosis (GD). We investigated the presence of GD and elucidated its correlation with Fontan pathophysiology. Methods and Results Gut microbiomes of 155 consecutive patients with Fontan pathophysiology and 44 healthy individuals were analyzed using 16S rRNA sequencing of bacterial DNA extracted from fecal samples. GD was evaluated on the basis of α and ß diversities of the gut microbiome and was compared with natural log‐transformed C‐reactive protein, hemodynamics, von Willebrand factor antigen (a bacterial translocation marker), Mac‐2 binding protein glycosylation isomer (a liver fibrosis indicator), peak oxygen uptake, and heart failure hospitalization. Patients with Fontan exhibited GD in terms of α and ß diversities as compared with controls (P<0.01). Reduced α diversity was associated with a failed hemodynamic phenotype, hypoxia, high natural log‐transformed C‐reactive protein levels, and elevated von Willebrand factor antigen and Mac‐2 binding protein glycosylation isomer levels (P<0.05–0.01). In addition to elevated von Willebrand factor antigen and hypoxia, decreased α diversity was independently correlated with a high natural log‐transformed C‐reactive protein level (P<0.05), which was associated with liver imaging abnormalities and a heightened risk of heart failure hospitalization (P<0.01 for both). Conclusions Patients with Fontan pathophysiology exhibited GD compared with healthy individuals, and GD was linked to failed hemodynamics and systemic inflammation with a poor prognosis. Therefore, GD may play a pivotal role in a failing Fontan status, including Fontan‐associated liver disease, through GD‐associated systemic inflammation.https://www.ahajournals.org/doi/10.1161/JAHA.124.034538FontanFontan‐associated liver diseasegut dysbiosisheart failurehemodynamics
spellingShingle Hideo Ohuchi
Ryotaro Asano
Aki Mori
Tomohiko Ishibashi
Daisuke Motooka
Michikazu Nakai
Yoshikazu Nakaoka
Gut Dysbiosis in Patients With Fontan Circulation
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Fontan
Fontan‐associated liver disease
gut dysbiosis
heart failure
hemodynamics
title Gut Dysbiosis in Patients With Fontan Circulation
title_full Gut Dysbiosis in Patients With Fontan Circulation
title_fullStr Gut Dysbiosis in Patients With Fontan Circulation
title_full_unstemmed Gut Dysbiosis in Patients With Fontan Circulation
title_short Gut Dysbiosis in Patients With Fontan Circulation
title_sort gut dysbiosis in patients with fontan circulation
topic Fontan
Fontan‐associated liver disease
gut dysbiosis
heart failure
hemodynamics
url https://www.ahajournals.org/doi/10.1161/JAHA.124.034538
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AT daisukemotooka gutdysbiosisinpatientswithfontancirculation
AT michikazunakai gutdysbiosisinpatientswithfontancirculation
AT yoshikazunakaoka gutdysbiosisinpatientswithfontancirculation