Work

Reduction in microbiota-derived short-chain fatty acids contributes to the pathogenesis of pulmonary arterial hypertension

Year: 2026

Type: article

Abstract: Pulmonary arterial hypertension (PAH) is a progressive and fatal cardiopulmonary disorder, with growing evidence implicating proinflammatory gut dysbiosis in its pathogenesis. Fast growing broiler chickens ( Gallus gallus ) spontaneously develop PAH with histopathological features that closely resemble those of the human disease, providing a robust translational model. Gut microbiota composition in PAH-afflicted broilers was compared to that of healthy controls to identify disease-associated microbial alterations. Microbiota depletion was achieved using a broad-spectrum antibiotic cocktail, and oral supplementation with calcium acetate, a short-chain fatty acid (SCFA) salt, was administered to assess therapeutic potential. Pulmonary cytokine expression was measured to evaluate inflammation. PAH-afflicted broilers exhibited gut microbial alterations similar to those observed in human patients, characterized by a reduction in bacterial genera involved in the production of anti-inflammatory metabolites, particularly SCFAs, and an increase in arginine- and tryptophan-producing taxa. Microbiota depletion selectively enriched SCFA-producing bacteria and prevented the onset of PAH. Calcium acetate supplementation significantly mitigated disease progression and reduced pulmonary expression of proinflammatory cytokines. These findings establish a causal relationship between microbiome-derived metabolites and pulmonary vascular remodeling, supporting SCFA-based interventions as a promising therapeutic strategy for PAH.

Source: Respiratory Research

DOI: 10.1186/s12931-026-03591-9

Authors: Hamza Imtiaz, Rui Liu, Qing-Hao Li, Chun-Zhen Zhou, Yi-Tian Ying, Xun Tan

Institutions: Zhejiang University, Zhejiang Chinese Medical University

Language: English

Topic: Pulmonary Hypertension Research and Treatments

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,490