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自闭症儿童粪便微生物群移植后沿肠-脑轴的小鼠品系特异性反应。

Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism.

作者信息

Prince Naika, Peralta Marzal Lucia N, Roussin Léa, Monnoye Magali, Philippe Catherine, Maximin Elise, Ahmed Sabbir, Salenius Karoliina, Lin Jake, Autio Reija, Adolfs Youri, Pasterkamp R Jeroen, Garssen Johan, Naudon Laurent, Rabot Sylvie, Kraneveld Aletta D, Perez-Pardo Paula

机构信息

Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France.

出版信息

Gut Microbes. 2025 Dec;17(1):2447822. doi: 10.1080/19490976.2024.2447822. Epub 2025 Jan 7.

DOI:10.1080/19490976.2024.2447822
PMID:39773319
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11730631/
Abstract

Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.

摘要

有几个因素与自闭症谱系障碍(ASD)的病理生理学相关;然而,该病症的分子机制仍然未知。由于肠道问题和肠道微生物群失调与ASD的发展和严重程度有关,最近的研究集中在阐明微生物群-肠道-脑轴的参与情况。本研究旨在探索肠道微生物群可能影响ASD的机制。简而言之,我们在用来自ASD儿童或其神经典型同胞的样本进行人类粪便微生物群移植(hFMT)之前,耗尽了常规雄性BALB/cAnNCrl(Balb/c)和C57BL/6J(BL/6)小鼠的微生物群。我们发现小鼠品系对ASD hFMT有特异性反应。值得注意的是,Balb/c小鼠表现出探索和社交行为减少,并显示出肠道、全身和中枢炎症的证据,同时伴有代谢变化。BL/6小鼠在hFMT后变化较小。我们的结果表明,仅肠道微生物群就能诱导类似ASD行为的变化,并突出了在研究像ASD这样的多因素病症时选择小鼠品系的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/586e/11730631/cdef651eaf5d/KGMI_A_2447822_F0008_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/586e/11730631/cdef651eaf5d/KGMI_A_2447822_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/586e/11730631/9b3e5647115c/KGMI_A_2447822_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/586e/11730631/db801519e15b/KGMI_A_2447822_F0002_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/586e/11730631/3618e1750622/KGMI_A_2447822_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/586e/11730631/b3b1bed81f45/KGMI_A_2447822_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/586e/11730631/6275a2c50458/KGMI_A_2447822_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/586e/11730631/41fa3b0f7d05/KGMI_A_2447822_F0007_OC.jpg
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本文引用的文献

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Acta Pharmacol Sin. 2024 Aug;45(8):1591-1603. doi: 10.1038/s41401-024-01268-x. Epub 2024 Apr 8.
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Gut microbial and clinical characteristics of individuals with autism spectrum disorder differ depending on the ecological structure of the gut microbiome.自闭症谱系障碍患者的肠道微生物和临床特征因肠道微生物组的生态结构而异。
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Gut microbiome and serum amino acid metabolome alterations in autism spectrum disorder.
自闭症谱系障碍中肠道微生物组和血清氨基酸代谢组的改变。
Sci Rep. 2024 Feb 19;14(1):4037. doi: 10.1038/s41598-024-54717-2.
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Effects of a Mix on Behavioural, Biochemical, and Gut Microbial Outcomes of Male Mice following Chronic Restraint Stress.混合处理对慢性束缚应激雄性小鼠行为、生化和肠道微生物的影响。
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