The characteristics of oral, and gut microbiota in patients with congenital heart disease associated with pulmonary arterial hypertension

Background The cause of congenital heart disease associated with pulmonary arterial hypertension(CHD-PAH) remains largely unknown. The oral-gut microbiota axis plays a crucial role in cardiometabolic health. Objective To investigate the characteristics of oral, and gut microbiome in adult patients with CHD-PAH. Methods The study included control group, CHD without PAH group(CHD-NO-PAH), dynamic CHD-PAH group(CHD-PAH-D), and resistant CHD-PAH group (CHD-PAH-R). Saliva, and stool samples were collected. Metagenomic high-throughput sequencing was used to analyze the composition and function of microbes. Results In the oral microbiome, compared with the control group(n=37), CHD patients (n=134) showed a higher relative abundance of bacteria such as Alloprevotella and Abiotrophia. Compared with the CHD-NO-PAH group(n=51), the CHD-PAH group(n=83) had a significant increase in the abundance of Rothia(especially R. mucilaginosa), while the abundance of Neisseria and Haemophilus decreased. Further stratification showed that in the CHD-PAH-R group(n=44), the abundance of Actinomycetales/Actinomycetaceae and Prevotella multiformis was higher, while in the CHD-PAH-D group(n=39), the abundance of Desulfomicrobium orale and Propionibacterium acidifaciens increased. The oral microbiome of CHD patients showed functional changes, with significant alterations in the gene expression of pyrimidine dNTP de novo synthesis and O-glycan modification pathways. The abundance of microbes such as Veillonella and Prevotella were positively correlated with these pathways. In the gut microbiome, compared with the control group(n=33), the CHD group(n=121) showed a significant increase in the relative abundance of Actinobacteria and Coriobacteriia, while the control group was dominated by Clostridia. Compared with the CHD-NO-PAH group(n=43), the CHD-PAH group (n=78) had a higher relative abundance of Actinobacteria, Coriobacteriia, and Blautia_obeum. Further stratification showed that the CHD-PAH-R group(n=42) was mainly enriched with Actinobacteria and Coriobacteriia, while the CHD-PAH-D group(n=38) was primarily enriched with Bacteroidetes. In the CHD group, gene expression levels in several metabolic pathways, such as sucrose degradation and 1,5-anhydro-D-fructose degradation, decreased. Compared with the CHD-NO-PAH group, the CHD-PAH group showed a general decrease in gene expression in multiple metabolic pathways, involving carbohydrate metabolism, nucleotide metabolism, and vitamin metabolism. In the intersection microbiota analysis of the oral, and gut microbiomes, it was found that the CHD-PAH-R group had a significantly higher number of intersecting microbiota, possibly indicating microbial displacement in this group. Conclusion The composition and function of the oral, and gut microbiomes in CHD-PAH patients have undergone significant changes.The oral-gut microbiota axis may plays a crucial role in the pathogenesis and progression of CHD-PAH.