Inulin alleviates chronic ketamine-induced impairments in memory and prepulse inhibition by regulating the gut microbiota, inflammation, and kynurenine pathway.
Zhilong Xu, Haoyang Lu, Canrun Hu, Yuguan Wen, Dewei Shang, Tongying Gan, Zhihao Guo, Lijing Dai, Yayan Luo
International journal of biological macromolecules March 1, 2025 DOI: 10.1016/j.ijbiomac.2025.139503 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice (implied by the experimental context) |
| Interventions | Ketamine Inulin |
| Duration | 14 days |
| Topics | Ketamine Esketamine |
| Keywords | Gut microbiota Inulin Gut-brain axis Cognitive health Dietary fiber Microbiome research |
| Citations | 14 |
| Key findings | Inulin treatment alleviates chronic ketamine-induced cognitive impairments by restoring gut microbiota, reducing inflammation, and inhibiting the tryptophan-kynurenine-kynurenic acid pathway. |
Abstract
Chronic ketamine administration causes cognitive impairments similar to those observed in schizophrenia. Growing evidence suggests that patients with schizophrenia show alterations in gut microbiota, which is associated with cognitive impairments. Inulin could regulate gut microbiota. However, it is unclear whether chronic ketamine exposure causes cognitive impairments by mediating gut microbiota and whether inulin ameliorates these impairments. In this study, we found that chronic ketamine exposure for 14 days induced gut dysbiosis, thereby increasing gut permeability, upregulating LPS-activated TLR4-NF-κB-NLRP3 inflammatory pathway, causing hippocampal neuroinflammation and neuronal damage, activating tryptophan (TRP)-kynurenine (KYN)-kynurenic acid (KYNA) pathway in the hippocampus, peripheral serum, and feces, and thus leading to deficits in recognition memory and prepulse inhibition (PPI). In addition, inulin treatment restored gut dysbiosis by increasing the abundance of Turicibacter and Ileibacterium and decreasing the abundance of Alistipes, Alloprevotella, Desulfovibrio, and Parasutterella, which may improve gut barrier damage by upregulating tight junction protein expression, suppress LPS-mediated TLR4-NF-κB-NLRP3 inflammatory pathway to reduce neuroinflammation and neuronal damage, inhibit TRP-KYN-KYNA metabolism pathway, and thus alleviate chronic ketamine-associated impairments in PPI and memory. Our findings provide additional evidence that inulin treatment is a potential intervention strategy for treating chronic ketamine-associated cognitive impairments and cognitive deficits in schizophrenia.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 2
- Antidepressant effect of repeated ketamine administration on kynurenine pathway metabolites in patients with unipolar and bipolar depression. Brain, Behavior, and Immunity November 2018
- Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers Schizophrenia Research November 14, 2015