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