Insights on the Gut-Mesentery-Lung Axis in Pulmonary Arterial Hypertension: A Poorly Investigated Crossroad

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by the hyperproliferation of vascular cells, including smooth muscle and endothelial cells. Hyperproliferative cells eventually obstruct the lung vasculature, leading to irreversible lesions that collectively drive pulmonary pressure to life-threatening levels. Although the primary cause of PAH is not fully understood, several studies have indicated it results from chronic pulmonary inflammation, such as observed in response to pathogens' infection. Curiously, infection by the intravascular parasite Schistosoma mansoni recapitulates several aspects of the widespread pulmonary inflammation that leads to development of chronic PAH. Globally, >200 million people are currently infected by Schistosoma spp., with about 5% developing PAH (Sch-PAH) in response to the parasite egg-induced obliteration and remodeling of the lung vasculature. Before their settling into the lungs, Schistosoma eggs are released inside the mesenteric veins, where they either cross the intestinal wall and disturb the gut microbiome or migrate to other organs, including the lungs and liver, increasing pressure. Spontaneous or surgical liver bypass via collateral circulation alleviates the pressure in the portal system; however, it also allows the translocation of pathogens, toxins, and antigens into the lungs, ultimately causing PAH. This brief review provides an overview of the gut-mesentery-lung axis during PAH, with a particular focus on Sch-PAH, and attempts to delineate the mechanism by which pathogen translocation might contribute to the onset of chronic pulmonary vascular diseases.