Carolina Gubert, Geraldine Kong, Sheida Shadani, Sasha Connell, Bethany A Masson, Nicholas van de Garde, Vinod K Narayana, Thibault Renoir, Anthony J Hannan
{"title":"益生元在精神分裂症小鼠模型中拯救肠道微生物失调并增强认知和胃肠功能。","authors":"Carolina Gubert, Geraldine Kong, Sheida Shadani, Sasha Connell, Bethany A Masson, Nicholas van de Garde, Vinod K Narayana, Thibault Renoir, Anthony J Hannan","doi":"10.1093/schbul/sbaf056","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Schizophrenia is a devastating psychiatric disorder characterized by positive (eg, hallucinations) and negative (eg, reduced motivation) symptoms, and cognitive deficits. Chronic gastrointestinal tract issues exist as comorbid symptoms of schizophrenia. Recent findings indicate the involvement of the microorganisms that inhabit the gut, the microbiota (and the broader microbiome which also includes microbial genomes, etc.) in schizophrenia pathogenesis. In the present study, we hypothesized that chronic administration with prebiotics fructooligosaccharide and galactooligosaccharide (FOS and GOS; a combination used clinically for other disorders) would restore gut microbiome composition of the metabotropic glutamate receptor 5 (mGlu5) knockout (KO) mouse model of schizophrenia, which we previously demonstrated to exhibit gut dysbiosis.</p><p><strong>Study design: </strong>We assessed the impact of prebiotics on gut microbiome composition and function, as well as the gastrointestinal function and schizophrenia-like phenotype of mGlu5 KO mice and wild-type littermates. We administered a combination of the prebiotics FOS and GOS, vs vehicle control administration, in both the mouse model of schizophrenia and wild-type littermates.</p><p><strong>Study results: </strong>The present study firstly corroborated the altered gut microbiome composition in the mGlu5 KO mouse model of schizophrenia. Importantly, we have revealed an altered microbial metabolic profile. We have also shown that the prebiotics we administered were not only able to rescue these gut microbiome changes but also had additional beneficial effects including cognitive enhancement and improved gastrointestinal function.</p><p><strong>Conclusion: </strong>These preclinical findings indicate that prebiotics, such as the combination of FOS and GOS used in the present study, may have therapeutic potential in schizophrenia as an add-on intervention with an exceptional safety profile.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prebiotics Rescue Gut Microbiome Dysregulation and Enhance Cognitive and Gastrointestinal Function in a Mouse Model of Schizophrenia.\",\"authors\":\"Carolina Gubert, Geraldine Kong, Sheida Shadani, Sasha Connell, Bethany A Masson, Nicholas van de Garde, Vinod K Narayana, Thibault Renoir, Anthony J Hannan\",\"doi\":\"10.1093/schbul/sbaf056\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and hypothesis: </strong>Schizophrenia is a devastating psychiatric disorder characterized by positive (eg, hallucinations) and negative (eg, reduced motivation) symptoms, and cognitive deficits. Chronic gastrointestinal tract issues exist as comorbid symptoms of schizophrenia. Recent findings indicate the involvement of the microorganisms that inhabit the gut, the microbiota (and the broader microbiome which also includes microbial genomes, etc.) in schizophrenia pathogenesis. In the present study, we hypothesized that chronic administration with prebiotics fructooligosaccharide and galactooligosaccharide (FOS and GOS; a combination used clinically for other disorders) would restore gut microbiome composition of the metabotropic glutamate receptor 5 (mGlu5) knockout (KO) mouse model of schizophrenia, which we previously demonstrated to exhibit gut dysbiosis.</p><p><strong>Study design: </strong>We assessed the impact of prebiotics on gut microbiome composition and function, as well as the gastrointestinal function and schizophrenia-like phenotype of mGlu5 KO mice and wild-type littermates. We administered a combination of the prebiotics FOS and GOS, vs vehicle control administration, in both the mouse model of schizophrenia and wild-type littermates.</p><p><strong>Study results: </strong>The present study firstly corroborated the altered gut microbiome composition in the mGlu5 KO mouse model of schizophrenia. Importantly, we have revealed an altered microbial metabolic profile. We have also shown that the prebiotics we administered were not only able to rescue these gut microbiome changes but also had additional beneficial effects including cognitive enhancement and improved gastrointestinal function.</p><p><strong>Conclusion: </strong>These preclinical findings indicate that prebiotics, such as the combination of FOS and GOS used in the present study, may have therapeutic potential in schizophrenia as an add-on intervention with an exceptional safety profile.</p>\",\"PeriodicalId\":21530,\"journal\":{\"name\":\"Schizophrenia Bulletin\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2025-05-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Schizophrenia Bulletin\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/schbul/sbaf056\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Schizophrenia Bulletin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/schbul/sbaf056","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Prebiotics Rescue Gut Microbiome Dysregulation and Enhance Cognitive and Gastrointestinal Function in a Mouse Model of Schizophrenia.
Background and hypothesis: Schizophrenia is a devastating psychiatric disorder characterized by positive (eg, hallucinations) and negative (eg, reduced motivation) symptoms, and cognitive deficits. Chronic gastrointestinal tract issues exist as comorbid symptoms of schizophrenia. Recent findings indicate the involvement of the microorganisms that inhabit the gut, the microbiota (and the broader microbiome which also includes microbial genomes, etc.) in schizophrenia pathogenesis. In the present study, we hypothesized that chronic administration with prebiotics fructooligosaccharide and galactooligosaccharide (FOS and GOS; a combination used clinically for other disorders) would restore gut microbiome composition of the metabotropic glutamate receptor 5 (mGlu5) knockout (KO) mouse model of schizophrenia, which we previously demonstrated to exhibit gut dysbiosis.
Study design: We assessed the impact of prebiotics on gut microbiome composition and function, as well as the gastrointestinal function and schizophrenia-like phenotype of mGlu5 KO mice and wild-type littermates. We administered a combination of the prebiotics FOS and GOS, vs vehicle control administration, in both the mouse model of schizophrenia and wild-type littermates.
Study results: The present study firstly corroborated the altered gut microbiome composition in the mGlu5 KO mouse model of schizophrenia. Importantly, we have revealed an altered microbial metabolic profile. We have also shown that the prebiotics we administered were not only able to rescue these gut microbiome changes but also had additional beneficial effects including cognitive enhancement and improved gastrointestinal function.
Conclusion: These preclinical findings indicate that prebiotics, such as the combination of FOS and GOS used in the present study, may have therapeutic potential in schizophrenia as an add-on intervention with an exceptional safety profile.
期刊介绍:
Schizophrenia Bulletin seeks to review recent developments and empirically based hypotheses regarding the etiology and treatment of schizophrenia. We view the field as broad and deep, and will publish new knowledge ranging from the molecular basis to social and cultural factors. We will give new emphasis to translational reports which simultaneously highlight basic neurobiological mechanisms and clinical manifestations. Some of the Bulletin content is invited as special features or manuscripts organized as a theme by special guest editors. Most pages of the Bulletin are devoted to unsolicited manuscripts of high quality that report original data or where we can provide a special venue for a major study or workshop report. Supplement issues are sometimes provided for manuscripts reporting from a recent conference.