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帕金森病模型果蝇的微生物组改变对其发育有负面影响。

An altered microbiome in a Parkinson's disease model Drosophila melanogaster has a negative effect on development.

机构信息

Biomedical Sciences Program, College of Graduate Studies, Midwestern University, Glendale, AZ, USA.

Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA.

出版信息

Sci Rep. 2021 Dec 8;11(1):23635. doi: 10.1038/s41598-021-02624-1.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease, besides Alzheimer's Disease, characterized by multiple symptoms, including the well-known motor dysfunctions. It is well-established that there are differences in the fecal microbiota composition between Parkinson's disease (PD) patients and control populations, but the mechanisms underlying these differences are not yet fully understood. To begin to close the gap between description and mechanism we studied the relationship between the microbiota and PD in a model organism, Drosophila melanogaster. First, fecal transfers were performed with a D. melanogaster model of PD that had a mutation in the parkin (park) gene. Results indicate that the PD model feces had a negative effect on both pupation and eclosion in both control and park flies, with a greater effect in PD model flies. Analysis of the microbiota composition revealed differences between the control and park flies, consistent with many human studies. Conversely, gnotobiotic treatment of axenic embryos with feces-derived bacterial cultures did not affect eclosure. We speculate this result might be due to similarities in bacterial prevalence between mutant and control feces. Further, we confirmed a bacteria-potentiated impact on mutant and control fly phenotypes by measuring eclosure rate in park flies that were mono-associated with members of the fly microbiota. Both the fecal transfer and the mono-association results indicate a host genotype-microbiota interaction. Overall, this study concludes functional effects of the fly microbiota on PD model flies, providing support to the developing body of knowledge regarding the influence of the microbiota on PD.

摘要

帕金森病(PD)是仅次于阿尔茨海默病的第二常见神经退行性疾病,其特征是多种症状,包括众所周知的运动功能障碍。已经确定帕金森病(PD)患者和对照人群的粪便微生物群落组成存在差异,但这些差异的机制尚不完全清楚。为了开始缩小描述和机制之间的差距,我们在模式生物黑腹果蝇中研究了微生物群与 PD 之间的关系。首先,用携带 parkin(park)基因突变的 PD 黑腹果蝇模型进行粪便转移。结果表明,PD 模型粪便对对照和 park 果蝇的蛹化和羽化都有负面影响,对 PD 模型果蝇的影响更大。微生物群落组成的分析显示,对照和 park 果蝇之间存在差异,与许多人类研究一致。相反,用粪便衍生的细菌培养物对无菌胚胎进行生菌处理不会影响羽化。我们推测,这一结果可能是由于突变和对照粪便中细菌的流行率相似所致。此外,我们通过测量与果蝇微生物群单一相关的 park 果蝇的羽化率,证实了细菌对突变体和对照果蝇表型的增强作用。粪便转移和单一关联结果均表明宿主基因型-微生物群相互作用。总的来说,这项研究得出了果蝇微生物群对 PD 模型果蝇的功能影响,为微生物群对 PD 的影响的不断发展的知识体系提供了支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f94/8654912/ef1f162505fc/41598_2021_2624_Fig1_HTML.jpg

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