Differences in gut microbiota between onset and recovery from acute mountain sickness

Exposure to high altitudes often results in gastrointestinal disorders. This study aimed to identify probiotic strains that could alleviate such disorders. We conducted a microbiome analysis to investigate the differences in gut microbiota among volunteers during the acute response and acclimatization phases at high altitudes. A significant increase in the abundance of Faecalibacterium prausnitzii was observed during the acclimatization phase. To further explore this, we established a mouse model of intestinal barrier damage induced by high-altitude exposure. The results indicated that Faecalibacterium duncaniae (F. duncaniae) significantly reduced damage to the intestinal barrier and the decrease in 2-ketoglutaric acid levels in the cecal contents. Immunohistochemistry and TUNEL staining demonstrated that high-altitude exposure significantly decreased the expression of ZO-1 and occludin while increasing apoptosis in ileal tissues. In contrast, treatment with F. duncaniae alleviated the loss of ZO-1 and occludin, as well as the apoptosis induced by high-altitude exposure. Furthermore, 2-ketoglutaric acid also mitigated this damage, reducing the loss of occludin and apoptosis in mice. We conducted a transcriptome analysis to investigate the underlying mechanisms. The results indicated that high-altitude exposure significantly affects the calcium signaling pathway. Conversely, the administration of F. duncaniae significantly influenced the PPAR signaling pathway, mineral absorption, and the regulation of lipolysis in adipocytes. Additionally, the expression of Fos was markedly reduced with the administration of F. duncaniae. In conclusion, F. duncaniae mitigates hypoxia-induced intestinal barrier damage by increasing levels of 2-ketoglutaric acid and shows promise as a probiotic, ultimately aiding travelers in adapting to high-altitude environments.