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精神分裂症动物模型中人类粪便微生物群移植与肠道微生物组特征的关系:一项范围综述

Human-fecal microbiota transplantation in relation to gut microbiome signatures in animal models for schizophrenia: A scoping review.

作者信息

Singh Raghunath, Panganiban Kristoffer, Au Emily, Ravikumar Rekha, Pereira Sandra, Prevot Thomas D, Mueller Daniel J, Remington Gary, Agarwal Sri Mahavir, Verdu Elena F, Bercik Premysl, De Palma Giada, Hahn Margaret K

机构信息

Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.

Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

出版信息

Asian J Psychiatr. 2024 Dec;102:104285. doi: 10.1016/j.ajp.2024.104285. Epub 2024 Oct 24.

Abstract

More recently, attention has turned to the putative role of gut microbiome (GMB) in pathogenesis, symptomatology, treatment response and/or resistance in schizophrenia (SCZ). It is foreseeable that fecal microbiota transplantation (FMT) from SCZ patients (SCZ-FMT) to germ-free mice could represent a suitable experimental framework for a better understanding of the relationship between GMB and SCZ. Thus, we set out to identify literature (i) characterizing the GMB in animal models of SCZ, and (ii) employing SCZ-FMT into rodents to model SCZ in relation to behavioral and molecular phenotypes. Five studies examining animal models of SCZ suggest distinct GMB composition compared to respective control groups, which was correlated with SCZ-like behavioral phenotypes. Four additional studies investigated SCZ-FMT into rodents in relation to behavioral phenotypes, including spontaneous hyperlocomotion, social deficits, exaggerated startle response, and cognitive impairments, resembling those observed in SCZ patients. Mice receiving SCZ-FMT showed altered neurochemical and metabolic pathways in the brain. Animal models of SCZ have shown altered GMB composition, whereas reported behavioral and neurochemical alterations following FMT from patients into rodents suggest early face and construct validity for SCZ-FMT animal models. However, the predictive validity of these models remains to be validated.

摘要

最近,注意力已经转向肠道微生物群(GMB)在精神分裂症(SCZ)的发病机制、症状学、治疗反应和/或耐药性中所假定的作用。可以预见,将SCZ患者的粪便微生物群移植(FMT)(SCZ - FMT)到无菌小鼠体内可能是一个合适的实验框架,有助于更好地理解GMB与SCZ之间的关系。因此,我们着手确定相关文献:(i)描述SCZ动物模型中的GMB特征,以及(ii)将SCZ - FMT应用于啮齿动物,以模拟与行为和分子表型相关的SCZ。五项研究对SCZ动物模型进行了检验,结果表明与各自的对照组相比,GMB组成存在差异,这与类似SCZ的行为表型相关。另外四项研究调查了将SCZ - FMT应用于啮齿动物后的行为表型,包括自发运动亢进、社交缺陷、惊吓反应过度和认知障碍,这些与在SCZ患者中观察到的情况相似。接受SCZ - FMT的小鼠大脑中的神经化学和代谢途径发生了改变。SCZ动物模型显示GMB组成发生了变化,而报道的将患者的FMT应用于啮齿动物后的行为和神经化学改变表明SCZ - FMT动物模型具有初步的表面效度和结构效度。然而,这些模型的预测效度仍有待验证。

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