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发育性口吃小鼠模型中肠道微生物组成的非典型性。

Atypical gut microbiota composition in a mouse model of developmental stuttering.

机构信息

Department of Communication Sciences and Disorders, University of Delaware, Newark, DE, 19716, USA.

Department of Animal and Food Sciences, University of Delaware, Newark, DE, 19716, USA.

出版信息

Sci Rep. 2024 Oct 8;14(1):23457. doi: 10.1038/s41598-024-74766-x.

Abstract

Developmental stuttering is a complex neurodevelopmental disorder characterized by disfluent speech. It has been associated with mutations in genes involved in lysosomal enzyme trafficking. Mice with mutations in one such gene, Gnptab, exhibit atypical vocalizations analogous to stuttering in humans. This mouse model has enabled the study of various molecular mechanisms related to the disorder. Simultaneously, an increasing number of reports have suggested the role of gut microbiota in altered brain function and development in neurological disorders. In this study, we compared gut microbiota profiles from Gnptab mutant mice to wildtype control mice. Microbiome analysis demonstrated a distinct microbiota profile in Gnptab mutant mice. The most significant alteration was an increased relative abundance of Akkermansia, a genus of mucin degrading bacteria, which has previously been associated with multiple neurological disorders. Moreover, the altered microbiota profile of these mice was predicted to result in differences in abundance of several metabolic pathways, including short chain fatty acid and lipopolysaccharide synthesis. These pathways may play a role in the onset, progression and persistence of developmental stuttering. This is the first study to show a potential link between developmental stuttering and changes in the gut microbiota, laying the groundwork for a new research direction.

摘要

发展性口吃是一种复杂的神经发育障碍,其特征是言语不流畅。它与参与溶酶体酶运输的基因突变有关。在一个这样的基因 Gnptab 发生突变的小鼠中,表现出类似于人类口吃的非典型发声。这种小鼠模型使人们能够研究与该疾病相关的各种分子机制。与此同时,越来越多的报告表明,肠道微生物群在神经紊乱中改变大脑功能和发育中起作用。在这项研究中,我们比较了 Gnptab 突变小鼠和野生型对照小鼠的肠道微生物群图谱。微生物组分析表明 Gnptab 突变小鼠具有独特的微生物群图谱。最显著的改变是阿克曼氏菌(一种粘蛋白降解细菌)的相对丰度增加,阿克曼氏菌先前与多种神经紊乱有关。此外,这些小鼠的改变的微生物群图谱预计会导致几种代谢途径丰度的差异,包括短链脂肪酸和脂多糖的合成。这些途径可能在发展性口吃的发作、进展和持续中起作用。这是首次表明发展性口吃与肠道微生物群变化之间存在潜在联系的研究,为新的研究方向奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9a0/11461706/48531a57e15a/41598_2024_74766_Fig1_HTML.jpg

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