Ozone rectal insufflation mitigates chronic rapid eye movement sleep deprivation-induced cognitive impairment through inflammation alleviation and gut microbiota regulation in mice

A range of sleep disorders has the potential to adversely affect cognitive function. This study was undertaken with the objective of investigating the effects of ozone rectal insufflation (O 3 -RI) on cognitive dysfunction induced by chronic REM sleep deprivation, as well as elucidating possible underlying mechanisms. O 3 -RI ameliorated cognitive dysfunction in chronic REM sleep deprived mice, improved the neuronal damage in the hippocampus region and decreased neuronal loss. Administration of O 3 -RI may protect against chronic REM sleep deprivation induced cognitive dysfunction by reversing the abnormal expression of Occludin and leucine-rich repeat and pyrin domain-containing protein 3 inflammasome as well as interleukin-1β in the hippocampus and colon tissues. Moreover, the microbiota diversity and composition of sleep deprivation mice were significantly affected by O 3 -RI intervention, as evidenced by the reversal of the Firmicutes/Bacteroidetes abundance ratio and the relative abundance of the Bacteroides genus. In particular, the relative abundance of the Bacteroides genus demonstrated a pronounced correlation with cognitive impairment and inflammation. Our findings suggested that O 3 -RI can improve cognitive dysfunction in sleep deprivation mice, and its mechanisms may be related to regulating gut microbiota and alleviating inflammation and damage in the hippocampus and colon.