Gut microbiota influence high altitude pulmonary edema

High altitude pulmonary edema (HAPE) is a severe and potentially life-threatening illness. However, our understanding of its underlying mechanisms is limited, and there is still no definitive evidence to support the causal role of gut microbes in HAPE. In this study, it was found that during the onset and recovery of acute mountain sickness (AMS), the abundance of Klebsiella and Escherichia-Shigella decreased significantly, while the abundance of Bifidobacterium increased significantly. The study also found that Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) disrupted lipid metabolism in rat plasma and significantly increased lysophosphatidylcholines (LPCs) levels, which promoted the occurrence of HAPE in rats. Conversely, a synthetic composition consisting of Bifidobacterium, Lactiplantibacillus, fructooligosaccharides and isomaltose oligosaccharides significantly reduced the severity of HAPE. Further investigations revealed that LPCs could directly damage the cell membrane of human pulmonary microvascular endothelial cells (HPMECs) and human pulmonary alveolar epithelial cells (HPAEpiCs) under hypoxic conditions. This led to cell monolayer injury and increased permeability, which are key characteristics of HAPE. Therefore, LPCs could be a potential therapeutic target for HAPE. In summary, gut microbe-derived disruption of lipid metabolism could promote the occurrence of HAPE.