Background

Immunopathological concepts have been intensively discussed for schizophrenia. The polyriboinosinic–polyribocytidylic (PolyI:C) mouse model has been well validated to invasively study this disease. The intestinal microbiome exhibits broad immunological and neuronal activities. The relevance of microbiome alterations in the PolyI:C model to human schizophrenia should be explored.

Methods

Feces of offspring from mice mothers, who were administered to PolyI:C or NaCl (controls) at ED 9, were collected at PND 30 and 180 (PolyI:C and control mice (N = 32 each; half males and females). This was analyzed for bacterial 16S ribosomal DNA (rDNA) using a gut microbiome polymerase chain reaction (PCR) microarray tool.

Results

Differences were found in species richness of microbiome between animals of different ages (PND 30 and 180), but also between offspring from PolyI:C vs. NaCl treated mothers. In female mice at PND 30, the abundance of Prevotellaceae and Porphyromonadaceae was lower and that of Lactobacillales was higher, whereas in male mice at the same time point the abundance of four families of the Firmicutes phylum (Clostridia vadinBB60 group, Clostridiales Family XIII, Ruminococcaceae and Erysipelotrichaceae) was increased relative to the control group.

Limitations

No further analyses of cell types or cytokines involved in autoimmune gut and brain processes.

Conclusions

These finding seem to be similar to microbiome disturbances in patients with schizophrenia. The differential bacterial findings at day 30 (i.e., similar to the prodromal phase in patients with schizophrenia) correspond to the tremendous activation of the immune system with a strong increase in microglial cells which might be responsible for neuroplasticity reduction in cortical areas in patients with schizophrenia.

背景

精神分裂症的免疫病理学概念已被广泛讨论。聚核糖核苷-聚核糖胞苷 (PolyI:C) 小鼠模型已被充分验证可用于侵入性研究这种疾病。肠道微生物组表现出广泛的免疫和神经元活性。应该探讨 PolyI:C 模型中微生物组改变与人类精神分裂症的相关性。

方法

在 ED 9 被给予 PolyI:C 或 NaCl（对照）的小鼠母亲的后代粪便在 PND 30 和 180 时收集（PolyI:C 和对照小鼠（N  = 32 各；一半雄性和雌性）。这使用肠道微生物组聚合酶链反应 (PCR) 微阵列工具分析细菌 16S 核糖体 DNA (rDNA)。

结果

在不同年龄（PND 30 和 180）的动物之间，以及来自 PolyI:C 与 NaCl 处理的母亲的后代之间，发现微生物组的物种丰富度存在差异。在 PND 30 雌性小鼠中，Prevotellaceae和Porphyromonadaceae的丰度较低，而 Lactobacillales 的丰度较高，而在同一时间点，雄性小鼠中厚壁菌门 4 个科的丰度（Clostridia vadinBB60 group、Clostridiales Family XIII、Ruminococcaceae和丹毒科）相对于对照组增加。

限制

没有进一步分析涉及自身免疫性肠道和大脑过程的细胞类型或细胞因子。

结论

这些发现似乎与精神分裂症患者的微生物组紊乱相似。第 30 天的不同细菌发现（即，类似于精神分裂症患者的前驱期）对应于免疫系统的巨大激活和小胶质细胞的强烈增加，这可能是精神分裂症患者皮质区域神经可塑性降低的原因.