Multi-Omics Analysis of the Microbial Profile Characteristics Associated with Pulmonary Arterial Hypertension in Congenital Heart Disease

Dysregulation of immune and inflammatory cells around blood vessels and metabolic dysfunction are key mechanisms in the development of pulmonary arterial hypertension. The homeostasis of the human microbiome plays a crucial role in regulating immune responses and the progression of diseases. For pulmonary arterial hypertension associated with congenital heart disease involving body-lung shunt , the potential impact of the microbiome on the "gut-lung axis" remains underexplored. This study recruited individuals from the general population and patients with PAH-CHD. We performed differential analyses of metabolites and microbiota from both the gut and lower respiratory tract for these two groups. The goal was to investigate the "gut-lung axis" microbiome and metabolome profiles in children with PAH-CHD and to analyze the interrelationships between these profiles. Ultimately, we aim to propose the potential value of these profiles in aiding diagnosis. The results indicated that the gut and pulmonary microbiota of children with PAH-CHD are characterized by an increased abundance of beneficial symbionts, which are closely linked to changes in the metabolome. Metabolite functional enrichment analysis revealed energy metabolism reprogramming in the PAH-CHD group, with active metabolic pathways associated with bile acid secretion and carnitine homeostasis. Moreover, the differential expression of metabolites was correlated with right heart function and growth development.