Altered gut microbial dynamics and the antivascular remodeling effect of carnosine in hypobaric hypoxic pulmonary hypertension rats

• Chronic hypobaric hypoxia induces significant alterations in gut microbiota and metabolome, with a notable decrease in fecal carnosine and its producer Ruminococcus bromii. • Carnosine levels inversely correlate with pulmonary arteriole media thickness, suggesting a protective role against vascular remodeling. • Therapeutic carnosine supplementation restores antioxidant defenses and attenuates pulmonary vascular remodeling without affecting right ventricular pressures. • In vitro, carnosine inhibits hypoxia-induced PASMC proliferation and migration, partly by suppressing Nrf2 accumulation.