The impact of prebiotic supplementation in a triple-hit rat model of schizophrenia

Mar 26, 2026Neuropharmacology

Effects of prebiotic supplements in a rat model combining three factors of schizophrenia

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Abstract

B-GOS monotreatment resulted in the highest improvement in cognition-related parameters in Wisket model rats, although it did not match the performance of control animals.

Schizophrenia is associated with cognitive deficits and increased stress sensitivity, possibly linked to gut microbiome disturbances.
Wisket model rats displayed greater vulnerability to stress induced by immobilization compared to control rats.
Clozapine and B-GOS treatments improved stress responses and cognitive performance in Wisket rats.
A combination of clozapine and B-GOS produced the most significant effects on behavior.
Fecal microbiota composition differed significantly among treatment groups, with certain bacterial taxa correlating with behavioral outcomes.

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Schizophrenia is associated with cognitive deficits and higher stress sensitivity, potentially related to gut-brain axis disturbances, partially due to dysbiosis. To ascertain this phenomenon, we aimed to evaluate these behavioral phenotypes in association with microbiota profile in the triple-hit Wisket rat model of schizophrenia. Furthermore, as a bidirectional approach, the effects of clozapine (CLO) and/or prebiotic (galactooligosaccharide, B-GOS) treatment were also investigated. Male Wistar (control) and Wisket rats were treated for 3 weeks: CLO or its vehicle was administered intraperitoneally, while B-GOS or water was provided ad libitum in drinking bottle. The food-rewarded Ambitus test was used to assess cognition-related behaviors before and during the third week of the treatment. Afterwards, fecal samples were collected to analyse microbiota composition, and smooth muscle electromyography was performed to assess immobilization-induced stress response. B-GOS monotreatment resulted in the highest improvement in cognition-related parameters in Wisket model rats; however, it never reached the performance of control animals. Wisket animals showed higher vulnerability to immobilization-induced stress condition. This group-difference disappeared by each pharmacological treatment, with the most prominent effect of the CLO + B-GOS combination treatment. β-diversity analysis revealed an overall compositional difference of fecal microbiota between treatment groups. Several taxa associated with schizophrenia-model or treatment were significantly correlated with behavioral parameters. Consistent with clinical findings, cognitive impairment with increased stress sensitivity were highlighted in Wisket model rats. To our knowledge, this is the first study on B-GOS prebiotic in a triple-hit schizophrenia model, suggesting microbiome-targeted therapy may aid some schizophrenia-related symptoms.

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The impact of prebiotic supplementation in a triple-hit rat model of schizophrenia

Abstract

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