Acute Hypoxic Exposure May Contribute to Depressive-Like Behaviors in Mice Through Disruption of Gut Microbiota Homeostasis.

Background: Depression represents a major global disease burden. High-altitude hypoxia is closely associated with an increased incidence of depressive symptoms; however, the underlying mechanisms remain unclear. Methods: In this study, mice were subjected to 7 days of hypoxic exposure simulating high-altitude environments at 3000 m (14.4% O Results: Hypoxic exposure induced depressive-like behaviors, as well as colonic and hippocampal tissue damage. It also exacerbated inflammation and oxidative stress, reduced gut microbiota diversity, disrupted tryptophan metabolism, decreased cortical neurotransmitter levels and brain-derived neurotrophic factor (BDNF), and increased the immunofluorescence density of hippocampal neuron-glial antigen 2 and oligodendrocyte transcription factor 2. These effects exhibited an intensity-toxicity relationship. Conclusions: Acute hypoxia is associated with gut microbiota imbalance, disrupted tryptophan metabolism, inflammatory responses, and dysfunction of the HPA axis, alongside negative emotional states. These multidimensional alterations are strongly correlated, suggesting a potential regulatory network involving the gut microbiota-tryptophan metabolism axis in hypoxia-induced emotional changes.