Gut-Lung Microbiome Axis: Altered Gut Microbial Signatures in Patients with Pulmonary Arterial Hypertension in the context of Iron deficiency

Background: Iron deficiency (ID), frequently observed in pulmonary arterial hypertension (PAH) patients, is linked to worse outcomes. Growing evidence also highlights a potential role of gut microbiota dysbiosis in PAH pathogenesis and also ID. Hence, we aimed to characterize the gut microbiome of PAH patients with and without ID and healthy controls. Methods: Stool samples (n=85) were collected from 42 patients divided into 14 PAH patients with ID (PAH-ID), 13 without (PAH-noID), and 15 matched healthy controls (HC). ID was defined by either recorded ID anemia in the past 3 years or clinical indication for i.v. iron supplementation. Samples were collected before and after a standardized iron absorption test with 200 mg iron (II) after an overnight fast. Amplicon libraries were prepared via the amplification of the V4 region of the 16S ribosomal gene. The quality control of sequenced reads (Illumina MiSeq) was performed using our custom pipeline, which incorporates DADA2 for the generation of ASVs (Amplicon Sequence Variants). Alpha- and beta-diversity metrics, hierarchical clustering and differential abundance were computed using different microbiome R packages (Vegan, PhyloSeq, DESeq2 and microeco). Results: The two PAH patient groups showed significantly different alpha diversity before the test. Beta diversity analysis demonstrated distinct microbial community structures between patient and control groups. Bacterial ecotypes were dominated by the most abundant taxa across groups with large intragroup variability. Conclusion: This study demonstrates significant gut microbiota dysbiosis in PAH patients compared to healthy controls. These findings highlight the gut microbiome’s potential role in PAH pathogenesis and open avenues for microbiota-targeted diagnostics or therapies. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany