Gut opportunistic pathogens contribute to high-altitude pulmonary edema by elevating lysophosphatidylcholines and inducing inflammation

The role of the gut microbiota in high-altitude pulmonary edema (HAPE) is currently unknown. This study found that intestinal <i>Klebsiella pneumoniae</i> and <i>Escherichia coli</i> contribute to HAPE by inducing inflammation and increasing lysophosphatidylcholine (LPC) levels under hypoxic conditions. Conversely, a synbiotic containing <i>Bifidobacterium</i>, <i>Lactiplantibacillus</i>, fructooligosaccharides, and isomaltose-oligosaccharides significantly reduced the severity of HAPE. Further investigation revealed that LPCs can cause damage and permeability to human pulmonary microvascular endothelial cell (HPMEC) and human pulmonary alveolar epithelial cell (HPAEpiC) monolayers under hypoxic conditions by disrupting cell membrane integrity. These findings contribute to the understanding of the pathogenesis of HAPE and will benefit populations living at high altitude or traveling from low to high altitude.