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。

IF 5.3 1区 医学 Q1 PSYCHIATRY
Carolina Gubert, Geraldine Kong, Sheida Shadani, Sasha Connell, Bethany A Masson, Nicholas van de Garde, Vinod K Narayana, Thibault Renoir, Anthony J Hannan
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引用次数: 0

摘要

背景与假设:精神分裂症是一种破坏性精神障碍,其特征是阳性(如幻觉)和阴性(如动机降低)症状以及认知缺陷。慢性胃肠道疾病是精神分裂症的合并症。最近的研究结果表明,居住在肠道中的微生物、微生物群(以及更广泛的微生物群,包括微生物基因组等)参与了精神分裂症的发病机制。在本研究中,我们假设长期服用益生元低聚果糖和低聚半乳糖(FOS和GOS);(一种临床上用于其他疾病的组合)将恢复代谢性谷氨酸受体5 (mGlu5)敲除(KO)精神分裂症小鼠模型的肠道微生物组组成,我们之前证明该模型表现出肠道生态失调。研究设计:我们评估了益生元对mGlu5 KO小鼠和野生型幼崽肠道微生物组成和功能的影响,以及胃肠道功能和精神分裂症样表型。我们在精神分裂症小鼠模型和野生型幼崽中施用了益生元FOS和GOS的组合,而不是对照施用。研究结果:本研究首次证实了精神分裂症mGlu5 KO小鼠模型中肠道微生物组组成的改变。重要的是,我们发现了微生物代谢谱的改变。我们还表明,我们给予的益生元不仅能够挽救这些肠道微生物组的变化,而且还具有额外的有益效果,包括增强认知能力和改善胃肠道功能。结论:这些临床前研究结果表明,益生元,如本研究中使用的FOS和GOS的组合,可能作为一种额外的干预措施在精神分裂症中具有治疗潜力,并且具有特殊的安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Schizophrenia Bulletin
Schizophrenia Bulletin 医学-精神病学
CiteScore
11.40
自引率
6.10%
发文量
163
审稿时长
4-8 weeks
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.
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