Antibiotic intervention exacerbated oxidative stress and inflammatory responses in SD rats under hypobaric hypoxia exposure

The gut microbiota plays a crucial role in maintaining host nutrition, metabolism, and immune homeostasis, particularly in extreme environmental conditions. However, the regulatory mechanisms of the gut microbiota in animal organisms hypobaric hypoxia exposure require further study. We conducted a research by comparing SD rats treated with an antibiotic (ABX) cocktail and untreated SD rats that were housed in a low-pressure oxygen chamber (simulating low pressure and hypoxic environment at 6000 m altitude) for 30 days. After the experiment, blood, feces, and lung tissues from SD rats were collected for analysis of blood, 16S rRNA amplicon sequencing, and non-targeted metabolomics. The results demonstrated that the antibiotic cocktail-treated SD rats exhibited elevated counts of neutrophil (Neu) and monocyte (Mon) cells, an enrichment of sulfate-reducing bacteria (SBC), reduced levels of glutathione, and accumulated phospholipid compounds. Notably, the accumulation of phospholipid compounds, particularly lysophosphatidic acid (LPA), lipopolysaccharide (LPS), and lysophosphatidylcholine (LPC), along with the aforementioned changes, contributed to heightened oxidative stress and inflammation in the organism. In addition, we explored the resistance mechanisms of SD rats in lowoxygen and low-pressure environments and found that increasing the quantity of the Prevotellaceae and related beneficial bacteria (especially Lactobacillus) could reduce oxidative stress and inflammation. These findings offer valuable insights into enhancing the adaptability of low-altitude animals under hypobaric hypoxia exposure.