Promising dawn in the management of pulmonary hypertension: The mystery veil of gut microbiota

The gut microbiota is a complex community of microorganisms inhabiting the intestinal tract, which plays a vital role in human health. It is intricately involved in the metabolism, and it also affects diverse physiological processes. The gut-lung axis is a bidirectional pathway between the gastrointestinal tract and the lungs. Recent research has shown that the gut microbiome plays a crucial role in immune response regulation in the lungs and the development of lung diseases. In this review, we present the interrelated factors concerning gut microbiota and the associated metabolites in pulmonary hypertension (PH), a lethal disease characterized by elevated pulmonary vascular pressure and resistance. Our research team explored the role of gut-microbiota-derived metabolites in cardiovascular diseases and established the correlation between metabolites such as putrescine, succinate, trimethylamine N-oxide (TMAO), and N, N, N-trimethyl-5-aminovaleric acid with the diseases. Furthermore, we found that specific metabolites, such as TMAO and betaine, have significant clinical value in PH, suggesting their potential as biomarkers in disease management. In detailing the interplay between the gut microbiota, their metabolites, and PH, we underscored the potential therapeutic approaches modulating this microbiota. Ultimately, we endeavor to alleviate the substantial socioeconomic burden associated with this disease. This review presents a unique exploratory analysis of the link between gut microbiota and PH, intending to propel further investigations in the gut-lung axis. With the rapid development of technologies, including metagenomic and nontargeted or targeted metabolomics, the knowledge of gut microbiota and their related metabolites is constantly growing. Dysfunctions of microorganisms are associated with cardiovascular diseases, and gut microbiota and its associated metabolites are also involved in the pathogenesis of pulmonary hypertension. In addition, pulmonary hypertension might result in the alteration of bacterial flora. Here, we provide a comprehensive landscape of gut microbiota and metabolites in pulmonary hypertension, emphasizing the interplay between microorganisms and hosts in modulating pulmonary hypertension.Highlightsimage The significant development in gut microbiota has brought an unprecedented paradigm for pulmonary hypertension (PH) management in recent years, which has delighted researchers and clinicians in precise disease control.The gut-lung axis is the bidirectional interaction between the gut and lung, which occurs through circulation, the nervous system, and other physiological processes, ultimately affecting the health of both the gut and the lung.We provided a comprehensive landscape of gut microbiota and its associated metabolites in PH, emphasizing the interplay between microorganisms and hosts in modulating PH.With the rapid development of technologies, including metagenomic and metabolomics on gut microbiota, the association of microorganisms and the human body will be untangled eventually, which will bring the dawn for disease cure followed by prognosis improvement among patients with PH.