寄生虫介导的小鼠模型行为和生物分子动力学改变
Parasite-mediated alteration of behaviour and biomolecular dynamics in a mouse model.
作者信息
Leonardi Steven Santino, Png Chin Wen, Bo Aye Sandi, Wong Peiyan, Rajagopal Iyer Vinaya, Tan Kevin Shyong-Wei
机构信息
Laboratory of Cellular and Molecular Parasitology, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
出版信息
Front Cell Infect Microbiol. 2025 Sep 10;15:1574660. doi: 10.3389/fcimb.2025.1574660. eCollection 2025.
INTRODUCTION
Blastocystis is a highly prevalent gut parasite whose pathogenicity remains unclear. Both beneficial and detrimental effects have been observed as a result of Blastocystis infection, including altered gut microbiota, metabolism, and gastrointestinal health. The parasite expresses a modified tryptophanase enzyme known as BhTnaA, which has the unique ability to metabolize indole to tryptophan. Enterochromaffin cells in the gut produce serotonin from tryptophan. These cells are innervated by the vagus nerve, which serves an essential role in mediating bidirectional signaling between the gut and brain. Perturbed serotonin signaling has been associated with disorders linked to gut-brain axis dysfunction, such as IBS and some mood disorders. Our study shows that Blastocystis can use BhTnaA to influence serotonin synthesis by enterochromaffin cells and in a mouse model, and that these effects result in alterations in mouse behaviour.
METHODS
We used RIN14B cells as an enterochromaffin cell model to determine whether BhTnaA upregulates serotonin synthesis and associated gene expression. Murine models colonized with multiple Blastocystis ST7 isolates were used to study altered serotonin metabolite levels in the gut. Analysis of mouse behavioral changes was done through the Light Box, Tail Suspension, and Open Field tests.
RESULTS
We demonstrated that the tryptophan produced by BhTnaA upregulates serotonin synthesis in EC cell models. In mice colonized with Blastocystis, increased tryptophan and serotonin levels were observed in the colon, a region of the gut inhabited by the parasites. Behavioral tests showed heightened anxiety in these mice, and a statistical correlation was identified between increases in the metabolites and observed anxiety behaviour.
DISCUSSION
Our study confirmed perturbation of gut tryptophan and serotonin levels by Blastocystis and showed a distinct correlation between this and increased anxiety in colonized mice. This provides a foundation for further investigation into the effects of these parasites on host physiology and the modulation of the gut-brain axis.
LSID IDENTIFIERS
: urn:lsid:zoobank.org:pub:EAED31FF-9880-4311-9E19-25257588FBB2.
引言
芽囊原虫是一种高度流行的肠道寄生虫，其致病性尚不清楚。芽囊原虫感染已观察到有益和有害的影响，包括肠道微生物群、新陈代谢和胃肠道健康的改变。该寄生虫表达一种名为BhTnaA的修饰色氨酸酶，它具有将吲哚代谢为色氨酸的独特能力。肠道中的肠嗜铬细胞从色氨酸产生血清素。这些细胞由迷走神经支配，迷走神经在介导肠道与大脑之间的双向信号传导中起重要作用。血清素信号紊乱与肠道-脑轴功能障碍相关的疾病有关，如肠易激综合征和一些情绪障碍。我们的研究表明，芽囊原虫可以利用BhTnaA影响肠嗜铬细胞的血清素合成，并在小鼠模型中发现这些影响导致小鼠行为改变。
方法
我们使用RIN14B细胞作为肠嗜铬细胞模型，以确定BhTnaA是否上调血清素合成和相关基因表达。用多种芽囊原虫ST7分离株定殖的小鼠模型用于研究肠道中血清素代谢物水平的变化。通过明箱、悬尾和旷场试验对小鼠行为变化进行分析。
结果
我们证明BhTnaA产生的色氨酸上调了肠嗜铬细胞模型中的血清素合成。在用芽囊原虫定殖的小鼠中，在寄生虫栖息的肠道区域结肠中观察到色氨酸和血清素水平升高。行为测试显示这些小鼠的焦虑加剧，并且在代谢物增加与观察到的焦虑行为之间确定了统计学相关性。
讨论
我们的研究证实了芽囊原虫对肠道色氨酸和血清素水平的干扰，并表明这与定殖小鼠焦虑增加之间存在明显的相关性。这为进一步研究这些寄生虫对宿主生理学的影响以及肠道-脑轴的调节提供了基础。
LSID标识符：urn:lsid:zoobank.org:pub:EAED31FF-9880-4311-9E19-25257588FBB2。
Zotero 插件