Selenium-Enriched Lacticaseibacillus rhamnosus Alleviates Hypobaric Hypoxia-Induced Brain Injury via Regulation of Gut Microbiota and Neurotransmitter Homeostasis.

Brain injury induced by hypobaric hypoxia is a concern for individuals exposed to high-altitude environments. This study evaluated the protective potential of prophylactic selenium-enriched Lacticaseibacillus rhamnosus (SeLRS) administration in C57BL/6 mice exposed to hypobaric hypoxia. Results showed that just 1 day of hypoxic exposure induced significant anxiety-like, depressive-like, and cognitive impairments, accompanied by hippocampal-amygdala structural damage, a decreased glutamate/gamma-aminobutyric acid ratio, and elevated oxidative stress and neuroinflammation. Critically, injury related abnormalities were still evident after 7 days of exposure, indicating that hypobaric hypoxia-associated brain injury was sustained under prolonged exposure conditions. Oral administration of SeLRS significantly improved behavioral and cognitive deficits, reduced neuroinflammation, attenuated hippocampal-amygdala damage. SeLRS administration was also associated with altered whole-brain glutamate content and amelioration of gut microbiota dysbiosis. 16S rRNA sequencing showed changes in the relative abundances of several taxa, including Muribaculum, Clostridium, Prevotella, and Akkermansia, which have previously been linked to neurotransmitter-related metabolic pathways. Overall, these findings support the potential of the complete SeLRS preparation as a probiotic-based nutritional strategy for mitigating hypobaric hypoxia-associated brain injury.