ABSTRACT Pulmonary hypertension (PH) is a complex and multifactorial disease that poses a significant clinical challenge. Despite extensive research, the underlying mechanisms of various risk factors remain elusive, and the therapeutic potential of food‐derived bioactive substances or gut microbial metabolites (GMM) requires further exploration. This study aimed to identify GMM with anti‐PH properties and elucidate their functional mechanisms. Through integrated analysis, the metabolite Urolithin A (UA) was identified as a key candidate, alongside four core genes shared between the gut microbiota and PH. Based on favorable drug‐likeness properties, UA was hypothesized to alleviate PH by modulating TNF‐associated pathways involved in cell proliferation, inflammation, and oxidative stress. The binding affinity between UA and its target TNF‐α was computationally predicted using molecular docking and molecular dynamics simulations and subsequently validated through surface plasmon resonance experiments. Our findings highlight the critical link between gut metabolites and vascular health, suggesting that UA holds promise as a novel dietary‐derived therapeutic agent for PH management.
Qu et al. (Sat,) studied this question.