Centre for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità (ISS), Rome, Italy.
Gastroenterology Division, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Foggia, Italy.
Neurosci Biobehav Rev. 2023 Apr;147:105105. doi: 10.1016/j.neubiorev.2023.105105. Epub 2023 Feb 18.
Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by deficits in social communication and interaction and repetitive/stereotyped behaviors. In recent years, the role of microbiota-gut-brain axis in ASD pathogenesis received growing attention, appearing as an attractive therapeutic target. We provide a comprehensive overview of changes in microbiota composition in ASD murine models so far identified, and summarize the therapeutic approaches targeting the microbiota on ASD-like neurobehavioral profile. Although alterations in microbiota composition have been observed in both genetic and environmental murine models of ASD, a clear microbiota profile shared by different ASD murine models has not been identified. We documented substantial discrepancies among studies (often within the same model), likely due to several confounding factors (from sex and age of animals to housing conditions). Despite these limitations, ASD animal models (under standardized conditions) remain a useful tool to evaluate (i) the beneficial effects of manipulations of gut microbiota on behavioral abnormalities; (ii) underlying neurobiological mechanisms related to gut-brain axis; and (iii) to identify optimal time windows for therapeutic interventions.
自闭症谱系障碍(ASD)是一种异质性神经发育障碍,其特征是社交沟通和互动以及重复/刻板行为存在缺陷。近年来,微生物群-肠-脑轴在 ASD 发病机制中的作用受到越来越多的关注,成为有吸引力的治疗靶点。我们全面概述了迄今为止在 ASD 鼠模型中发现的微生物群落组成的变化,并总结了针对类似 ASD 的神经行为特征的微生物群的治疗方法。尽管在 ASD 的遗传和环境鼠模型中都观察到了微生物群落组成的改变,但尚未确定不同 ASD 鼠模型共有的明确微生物群特征。我们记录了研究之间存在的大量差异(通常在同一模型中),这可能归因于几个混杂因素(从动物的性别和年龄到饲养条件)。尽管存在这些局限性,但 ASD 动物模型(在标准化条件下)仍然是评估以下方面的有用工具:(i)肠道微生物群的操作对行为异常的有益影响;(ii)与肠-脑轴相关的潜在神经生物学机制;和(iii)确定治疗干预的最佳时间窗口。