Inulin alleviates chronic ketamine-induced impairments in memory and prepulse inhibition by regulating the gut microbiota, inflammation, and kynurenine pathway.
International journal of biological macromolecules March 1, 2025 Zhilong Xu, Haoyang Lu, Canrun Hu et al. 14 citations
Chronic ketamine exposure for 14 days disrupts the gut microbiota, increases gut permeability, and activates an inflammatory pathway (TLR4-NF-κB-NLRP3) in the hippocampus, leading to neuroinflammation, neuronal damage, and activation of the tryptophan-kynurenine-kynurenic acid pathway in the hippocampus, blood, and feces. These changes result in deficits in recognition memory and prepulse inhibition (PPI). Treatment with inulin restores gut dysbiosis by increasing Turicibacter and Ileibacterium and decreasing Alistipes, Alloprevotella, Desulfovibrio, and Parasutterella, improves gut barrier integrity, suppresses the inflammatory pathway, reduces neuroinflammation and neuronal damage, and inhibits the tryptophan-kynurenine-kynurenic acid metabolism, thereby alleviating memory and PPI impairments. Inulin may be a potential intervention for cognitive deficits linked to chronic ketamine use or schizophrenia.