肠道微生态失调与精神分裂症的发生有关，精神分裂症是环境因素与遗传因素交互作用的结果。肠道微生态失调是否通过与易感基因交互作用增加个体患精神分裂症的风险知之甚少。本实验室前期的工作表明,神经调节素1(Nrg1)区域特异突变鼠呈现行为异常和突触功能缺失。在本项目中,我们利用精神分裂症易感基因Nrg1突变小鼠（Nrg1基因敲除及过表达）模型，拟从行为学、形态学、电生理和转录组学水平，分析肠道微生态失调对Nrg1突变小鼠产生的神经生物学效应，及其发育关键时间窗，并进一步利用益生菌修复肠道微生态失调诱发的精神分裂症，从而揭示肠道微生态失调与易感基因Nrg1在中枢神经系统中相互作用对神经功能的影响，并初步阐明其相应分子机制。本研究将有助于理解肠道微生态失调引发精神分裂症的神经机制，为开发新型益生菌调控肠道菌群实现精神分裂症的防治途径提供理论参考。

The link between gut dysbiosis and psychosis has been debated although there is epidemiological evidence that gut dysbiosis increases the risk of psychosis. The pathogenesis of schizophrenia and related mental illnesses likely involves multiple interactions between susceptibility genes of small effects and environmental factors. It isn’t clear whether schizophrenia patients carrying particular risk genes might be more sensitive to the psychosis-inducing effects of gut dysbiosis than other patients and healthy subjects. The experimental data in our lab showed that the ctoNrg1 mice, which mimic high levels of Nrg1 observed in forebrain regions of schizophrenic patients, exhibit schizophrenia relevant behavioral deficits and hypofunction of synaptic transmission. Here we will test the effects of gut dysbiosis on synaptic dysfunction and behavioral deficits of Nrg1 mutant mice (Nrg1 KO and ctoNrg1). First, effects of gut dysbiosis and the schizophrenia risk gene neuregulin-1 interaction in schizophrenia will be analyzed using behavioral, morphologic, electrophysiological and transcriptomics methods. Furthermore, the effects of gut dysbiosis will be studied in different critical time-windows. Finally, we will determine whether treatment of gut dysbiosis mice with probiotics corrects schizophrenia relevant behaviors. We propose that above experiment will help advance studies of neurobiological effects and the molecular mechanisms of gene-environment interplay. This study will provide the further understanding of the pathogenic mechanisms of gut dysbiosis in schizophrenia, and could possibly lead to a strategy for effective treatment of schizophrenia.