Department of Pediatric Cardiology National Cerebral and Cardiovascular Center Suita Japan.
Adult Congenital Heart Disease Center National Cerebral and Cardiovascular Center Suita Japan.
J Am Heart Assoc. 2024 Sep 17;13(18):e034538. doi: 10.1161/JAHA.124.034538. Epub 2024 Sep 9.
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.
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 (<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 (<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 (<0.05), which was associated with liver imaging abnormalities and a heightened risk of heart failure hospitalization (<0.01 for both).
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.
Fontan 病理生理学的发生机制是多因素的，可能包括肠道菌群失调（GD）。我们研究了 GD 的存在，并阐明了其与 Fontan 病理生理学的相关性。
采用 16S rRNA 测序技术，对 155 例 Fontan 病理生理学患者和 44 例健康个体的粪便样本中的细菌 DNA 进行分析，研究了肠道微生物组。根据肠道微生物组的α和β多样性评估 GD，并将其与自然对数转换的 C 反应蛋白、血液动力学、血管性血友病因子抗原（细菌易位标志物）、Mac-2 结合蛋白糖基化异构体（肝纤维化指标）、峰值摄氧量和心力衰竭住院进行比较。与对照组相比，Fontan 患者的肠道微生物组 α 和 β 多样性均存在 GD（<0.01）。α 多样性降低与血液动力学不良表型、缺氧、高自然对数转换的 C 反应蛋白水平以及血管性血友病因子抗原和 Mac-2 结合蛋白糖基化异构体水平升高相关（<0.05-0.01）。除了血管性血友病因子抗原升高和缺氧外，α 多样性降低还与高自然对数转换的 C 反应蛋白水平独立相关（<0.05），这与肝脏影像学异常和心力衰竭住院风险增加相关（<0.01）。
与健康个体相比，Fontan 病理生理学患者存在 GD，并且 GD 与不良血液动力学和全身炎症有关，预后不良。因此，GD 可能通过与 GD 相关的全身炎症在 Fontan 功能衰竭中发挥关键作用，包括与 Fontan 相关的肝病。
